Just like his original counterpart, he was voiced by Dan Povenmire.
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In his era, Jekyll was considered to be the evilest scientist of his time; he would have to get an angry mob's attention to do so. To that end, Jekyll created a machine-brewing potion that could turn someone into either a fairy princess or a monster. When the angry mob showed up at his house for their appointment, he drank the concoction the machine produced to show off the invention. However, the dial was turned to a fairy princess, thus ruining his chance to be a real evil genius. The mob left, annoyed with the supposed failure of Dr. Jekyll's invention. Realizing the problem, he quickly changed the dial to a monster and drank the concoction, this time, finally transforming into a monster. Delighted that he has finally succeeded, Jekyll ran through the village spreading evil, though he was actually doing childish pranks rather than just doing real evil havoc. However, during his reign of havoc, Jekyll ends up upsetting the platypus monster, who chases after him.
Later in the episode, Jekyll attends the monster ball, hoping to use his machine to help him win the contest, but ends up meeting the Platypus Monster again; immediately, the monster begins to beat him up. After asking for a time-out to go get a drink, Jekyll once again drinks his invention's brew but ends up turning himself into a fairy princess. Jekyll set the dial back to the monster again, but before he could get another drink, the Platypus Monster grabs him. While Heinz would later admit that he is unaware of Jekyll's fate, it's implied that the Platypus Monster has eaten Jekyll, as the platypus monster coughed out Jekyll's magic wand during the end of the episode.
- Although the Platypus Monster eats Jekyll alive, it is debatable if he survived or not. Possibly he indeed survived the Monster's belly, as if he would have been killed, any more Doofenshmirtz, like Heinz Doofenshmirtz, would have never existed. Otherwise, it must be possible that he was married before, had a child, and later divorced, similarly to Heinz's case with Charlene; meaning that he truly died when the Platypus Monster ate him.
- He is named after and inspired by Dr. Henry Jekyll, the title character and former self of Edward Hyde of the late Robert Louis Stevenson's 1886 novella Strange Case of Dr Jekyll and Mr Hyde.
- However, Jekyll Doofenshmirtz's monstrous form is more of an alternate transformation, rather than his repressed urges (like Edward Hyde).