Dr. Henry Jekyll/Mr. Edward Hyde is the dual title character of Strange Case of Dr Jekyll and Mr Hyde, a novella written by the Scottish author Robert Louis Stevenson that was first published in 1886. Henry Jekyll is a doctor who has covered up a secret life full of cruel deeds. He feels as if he is constantly battling within himself between what is good and what is evil, but has spent a great part of his life trying to repress evil urges that were not fitting for a man of his stature. After drinking a potion of his own creation, Jekyll is transformed into the smaller, younger, cruel, remorseless, evil Edward Hyde, representing the hidden side of Dr Jekyll's nature brought to the fore. Dr Jekyll has many friends and has a friendly personality, but as Mr Hyde, he becomes mysterious and violent. As time goes by, Mr Hyde grows in power. After taking the potion repetitively, he no longer relies upon it to unleash his inner demon i.e. his alter ego. Eventually, Mr Hyde grows so strong that Dr Jekyll becomes reliant on the potion to remain himself.

In "Stewie Loves Lois", Brian Griffin is so amazed at Stewie's personality change toward his mother Lois that he compares it to Jr. Jekyll and Mr. Sulu, the latter, played by George Takei was known for his rumored homosexuality which was confirmed shortly after the episode aired.