In the original script, Oswald was going to be the main antagonist, but was replaced with the Blot in order to avoid hurting his reputation by portraying him as an unlikable character.

During the ending, Spoiler:the Gremlins use a recolored model of Gus. Due to this, every Gremlin has Gus' hat and mustache.

Minnie Mouse was originally going to appear in the ending, where Oswald was to sneak in and interrupt her kiss to Mickey.

While Walt Disney created Oswald the Lucky Rabbit and the cartoons featuring him, Universal distributed them and owned the rights to the character. In 2006, in order to acquire the rights to use Oswald, Disney made a deal that included trading the services of sportscaster Al Michaels to Universal to get Oswald back.

There is some debate over the legitimacy of this deal, as there are no records of Oswald's debut cartoon - "Trolley Troubles" - having its copyright renewed by Universal when it should have in 1955, meaning that Oswald could have been a public domain character as far back as the 50s and it was likely just the trademark that was traded. This is something Disney would still end up utilizing as Oswald has made appearances in merchandising, commercials, and parks that would require trademark ownership, but would not likely inherently be required for a video game project. Oswald is unquestionably confirmed to be a public domain character as of 2023 following the 95-year anniversary of "Trolley Troubles".

In Tortooga, if the player helps Beluga Billy, he will give the player a sketch of a stop watch and say "It's dangerous to go alone! Take this." This is a reference to the original The Legend of Zelda.

Oswald's original love interest, Fanny, was set to appear in the game. She was dropped in favor of Oswald's last love interest, Ortensia.

When Mickey meets Oswald for the first time, Oswald is cleaning a little bunny doll of himself that is kept in a glass case. The doll itself is based on the very first product of Oswald the lucky rabbit, and was made when Walt Disney still owned the character. The doll itself is considered a collectible.

Originally Mickey's design would change based on how you played the game. Hero being good, Wastelander being anti-hero, and Scrapper being bad. Due to negative feedback of Scrapper Mickey's personality, the three designs were scrapped.

Many areas in the game are taken directly from areas of Disney Land and scenes in Disney animations.

The Lonesome Manor is not based on any one Haunted Mansion Ride but all of them. Plus, there are three cameos from past Disney characters. A painting of Chernabog (the demon from Night of Bald Mountain from the movie Fantasia), Madam Leona (the head in the Crystal Ball), and The Lonesome Ghosts (from Mickey Mouse Cartoons).

The gameplay design was inspired from the action of the old school The Legend of Zelda games, the platforming of Mario, and the RPG elements of Deus Ex.

On Mickey Junk Mountain (Wasteland version of the Matterhorn) you can see a number of old NES and SNES Mickey Mouse game cartridges made by Capcom.

There is a hidden room on Mickeyjunk Mountain containing a basketball backboard. It is a tribute to a secret half court in the peak of the Matterhorn Bobsleds ride at Disneyland which employees built for use between shifts.

At the end of the game, once Mickey gets back to his world, his calendar reads the date as "November 18th". This date is the release date of Steamboat Willie, the very first Mickey cartoon, November 18th 1928. November 18th was also the release date for Epic Mickey 2: The Power of Two in North America.