Mr. Hyde is shown looking for Jack Skellington in a pumpkin patch when he leaves. He also inquires about the Christmas custom of hanging a sock on the wall, wondering if it still had a foot in it.
Mr. Hyde is created when his alter-ego, Dr. Jekyll, makes a transformation serum. Hyde quickly takes over as the Warden of the asylum where Jekyll works, forcing him to become a prisoner. To make sure Jekyll does not escape, Hyde enlists an orderly at the asylum, named Poole, to keep watch over his other half.
Unbeknownst to Hyde, Jekyll begins growing a purple flower on the grounds of the asylum, which will serve as the final ingredient in a serum that will separate the doctor and Hyde into two separate people.
When Snow White, Prince Charming, Captain Hook, and Zelena arrive in the Land of Untold Stories, asking Jekyll for help in repairing the Apprentice's wand, they are imprisoned in the asylum by Poole. Hyde later visits them, believing they are doing the work of Rumplestiltskin. He starts to choke Hook, but stops when Snow tells him that they do not work for the Dark One, and that he stole magic from them to save his wife.
After returning to the prisoners later as Jekyll, and agreeing to fix the Apprentice's wand, his alter ego is caught by Poole, and is forced to drink the transformation serum, turning him back into Hyde. Hyde becomes preoccupied with the power of the wand, and realizes it can open a portal to the Land Without Magic. He uses this knowledge to steal Pandora's Box from Rumplestilskin, to use as leverage against him.
Later, at Jekyll's old home, the doctor is transformed into Hyde once again, after Poole catches him adding the flower to the separation serum. After Hyde takes over Jekyll's body again, he injects the serum into himself, separating Hyde from the doctor and giving them separate bodies. When Hyde begins to choke his former good half, Hook tackles Hyde, and Snow knocks him unconscious with Poole's taser. As Jekyll and the others escape into the city, Hyde corners them in an alley. Their confrontation is abruptly brought to a halt when pennies begin to rain down from the sky and a watery portal opens up. Everyone except Hyde manages to jump through the portal, returning to the Land Without Magic.
Later, back at the asylum, Hyde is confronted by Rumplestilskin, who came through the portal as everyone else was returning. Hyde tells Rumple that if he wants to see his wife and his unborn child again, Rumple will help him defeat Jekyll. Rumple begins to choke Hyde, telling him the only deal they will make will be that Hyde will be spared if he hands over Pandora's Box. Hyde begins to plead with Rumple telling him he can help the Dark One wake his wife from the Sleeping Curse. He says he learned information from being the Warden of the asylum, and knows of a place Rumple can go to get answers. When Rumple asks him where the place is, Hyde suggests they make a deal. Rumple agrees to hand over Storybrooke to Hyde in exchange for the information on how to wake Belle from the curse.
When Regina uses the Olympian Crystal to restore magic to Storybrooke, Hyde teleports there and thanks Regina for bringing the magic back. When Henry asks Hyde how he got there, Regina releases that Rumplestiltskin made a deal with Hyde. Hyde discloses the details of the deal, saying he provided Rumple with information in exchange for the town. He also tells Regina and Henry that he brought some friends along, so that their forgotten stories can play out in Storybrooke. When Regina tells Hyde she knows that he will lose in the end, due to how his story ends, Hyde tells her that darkness is not as easy to snuff out as she believes, and walks off.
- Mr. Hyde is based on the character the same name from the novel The Strange Case of Dr. Jekyll and Mr. Hyde by Robert Louis Stevenson; however, no mention of Dr. Jekyll appears in the movie.
- An animated version of Hyde appears in Mickey's Gala Premier, as Fredric March dressed as the character from the 1931 Paramount film Dr. Jekyll and Mr. Hyde.
- In the YouTube channel, The Cute Mario Bros, Mr. Hyde has a very big role as a main character, but he is called the risk.