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She is voiced by Mila Kunis, who also played the Wicked Witch of the West in Oz the Great and Powerful.
Meg is considered to be the "black sheep" of the Griffin Family who is often bullied, abused, and ignored. Because of this, she developed many insecurities that prompted to try to fit in with the popular crowd to no avail. She also mostly serves as the butt of Peter's jokes that leaves her humiliated.
However, things can get out of hand Meg gets pushed too far; this was shown in the episode "Dial Meg for Murder", where she was sent to prison for being in love with a convict, only to return as a juvenile delinquent who abuses her family in revenge for their treatment. Even in the episode "Seahorse Seashell Party", where she angrily voiced her objection over her family's behavior towards her, only for the other family's members to turn their rage on each other as Meg stood up for herself. However, she later apologizes upon realizing that the family needs a "lightning rod" to absorb the dysfunction. In the episode "Road to Rupert", Meg assaults a man for insulting her after a fender-bender, which actually impressed Peter and his friends a lot.
Despite being the scapegoat, there were a few times when Meg get a little recognition for the good things that she has done. In the episode "Peter's Sister", she meets her aunt Karen Griffin, who has proven to be abusive to Peter. At first, Meg finds Karen to be hilarious, but realizes that her treatment towards Peter is what made him the abusive man he is known today. As such, Meg helped Peter defeat Karen in a fight, and Peter apologizes to Meg for his treatment towards her, admitting that he was stupid to take out his pain on her. Ever since then, Peter started to show a little care towards Meg, even defending her from bullies in the episode "The Peter Principal". In the episode "Amish Guy", she and an Amish boy named Ezekiel developed genuine feelings for each other, despite their fathers' feud against each other. In the episode "Valentine's Day in Quahog", she went on a date with a boy named Toby, who tried to take her kidney to donate, though he later returns it to Meg before giving her a kiss at the end of the day, much to her delight.
- Her first villainous act & the only one with her original voice actress was in the episode "Love Thy Trophy". In the episode, she gets a job at a pancake house so she can buy herself an $1100 Prada purse. She lets the restaurateur, Flappy, believe that Stewie is her baby so she will get the job. She realizes that allowing customers to think Stewie is a crack-addicted baby and she is his single mother results in higher tips. Stewie plays along because he loves the restaurant's pancakes. A woman named Sandy Belford from Child Protective Services asks Flappy for Meg's address. On Spooner Street the neighbors fight over a missing trophy and Joe, Quagmire and Cleveland are quick to badmouth the Griffins, leading CPS to place Stewie in a foster home where he lives with kids from a variety of ethnic origins. The neighbors put their conflict aside to retrieve Stewie. When an espionage mission fails, they trade Meg's Prada bag for Stewie.
- In "Road to Rupert", Peter temporarily loses his license and it falls to Meg to have to drive him and all his drinking buddies around town. With her inebriated father and the guys tormenting her in the backseat with their childish antics, Meg understandably grows increasingly frustrated. But instead of kicking them all out or insisting that she won’t take that kind of abuse, she redirects her anger in the worst possible way. When she stops suddenly, the car behind her rear-ends Peter's car and when the other driver comes up to confront her, she gets out and beats him to a pulp. Yes, she was being harassed, but violence is no way to deal with it. In real life, she’d be looking at some major charges.
- In "Don't Make Me Over", after getting a makeover, Meg developed a career as a popular singer with her family as, but the fame and success caused her to be become more arrogant in nature, even defying Lois by claiming that she "is the band", causing more resentment towards the other family members. However, she abandons her career after being used by Jimmy Fallon during Saturday Night Live, though Peter beats up Fallon for laughing during sketches.
- In "Untitled Griffin Family History", Meg is charged for forcing herself upon a group of would-be captors.
- In "Barely Legal", she grew obsessed with the family dog Brian after a drunken kiss at the Junior Prom, even kidnapping him and attempting to rape him.
- In "Not All Dogs Go to Heaven", she becomes a born again Christian, but it actually brings out some of the worst in her. She attempts to convert Brian, who happens to be an ashiest. When he repeatdley refuses, she spreads word of Brian's atheism around Quahog, which generally hates atheists, making him a pariah. To add insult to injury, Brian is banned from every bar and convenience store in Quahog, making it impossible for him to drown his sorrows. Desperate, and suffering from delirium tremens (he hallucinates seeing several alcoholic beverages begging him to drink them), Brian fakes his repentance and convinces Meg to cease all hostilities against him so he can get back to drinking, but she takes him to burn books that are "harmful to God" (including On the Origin of Species by Charles Darwin, A Brief History of Time by Stephen Hawking, and a book titled Logic for First Graders). A disgusted Brian admits his bluff and attempts to convince Meg that what she is doing is wrong. When Meg refuses to listen, Brian points out to her that if there were truly a loving God, then he wouldn't have created Meg to have an attractive mother like Lois but have her to more physically resemble Peter, and that she wouldn't be brought into a world where everyone holds her in contempt. Feeling ashamed, Meg concedes to Brian's argument and apologizes for her behavior, confessing that she doesn't know how she can feel loved.
- In "Brian Griffin's House of Payne", she and Chris, knocked Stewie out cold, so badly, that his brain was showing. The two covered it up for a few months, before Peter found out. When he did, he threw Stewie under Lois' car, injuring him even worse, and blaming his concussion on Lois.
- In "Dial Meg for Murder", Meg was desperate enough to date a criminal. After serving time for harboring him, she started robbing Mort's Pharmacy and knocking Peter's teeth out and rapidly beating him; even doing the same to her rival Connie DiMico and her friends when they insulted her, which resulted her getting suspended from school.
- In "The Hand that Rocks the Wheelchair", she frames Bonnie for smuggling a gun through airport security and tries to take her place after becoming obsessed with Joe.
- In "April in Quahog", Meg was rumored to strangle stray cats.
- In "Seahorse Seashell Party", she finally stands up to her family and delivered some horrible truths to them, only for them to fall apart. This made her realize that she needed to be the lightning rod.
- In "Friends Without Benefits", she became obsessed with a boy whom she found out was gay and in love with Chris. In order to have closure she asked Chris to have sex with this boy and when he refused, she attempted to roofie him. Basically, she planned to have her brother raped and to turn her crush into his rapist. It's also revealed that she taught Chris how to poison squirrels during a family vacation.
- In "Chris Cross", she blackmailed Chris, after catching him stealing from Lois' purse. Her demands start off small (making Chris do her homework/clean her room, etc.) Basic sibling stuff. But then her requests get increasingly disturbed like stalk outside of planned parenthood, take the names of the girls who go inside, and then dial them up with some seriously messed up crank call material. She also reveals to Chris, or at least heavily implies, that she is an anti-Semite as she was part of a gang that vandalizes Anne Frank's house on an annual yearly basis, even though she's half-jewish. Basically, she goes way beyond a little sibling rivalry; what she does and wants is downright criminal. She also revealed to Chris did that even though he her Bidding, she still intended to sell him out.
- In "The Peter Principal", Meg (after a little encouragement from Esther, Ruth & Patty) uses Peter's power as the principal to get revenge on everybody she and her friends hated. At first, it was just bullies, but then she and her friends went mad with power and got her dad to punish boys who refused to go out with her and her friends.
- In "The D in Apartment 23", after Brian made a racially insensitive remark, the Griffin family is treated as pariahs by everyone. As such, Meg and Chris are treated as pariahs by the students, which provoked the two to engage in a fight against the students, killing them one by one before leaving in a huff.
- In "Crimes and Meg's Demeanor", Meg became an alcoholic and used a fake identity to buy it. She got herself in a lot of trouble, while drunk. She rebelled against her parents, got suspended for insulting transgenders, and stole the arc of the covenant, with her father.
- In "Trans-Fats", it's revealed that she kills people while wearing a wedding dress.
- Meg had a cameo on MTV's Good Vibes episode "Red Tuxedo". In addition, her voice actor Mila Kunis also appeared as herself.
- Meg explains to Lisa Simpson in "The Simpsons Guy" that when she gets upset, she beats up cats (causing Lisa to hide her cat Snowball II). She also cuts Lisa's name into her arm as a sign of friendship when Lisa gives Meg her saxophone, which Peter promptly throws into the trash.