- Celebrity Voice Actor: Guest voices for the show include John Stamos as Captain Salty Bones, Mickey Guyton as Wanda Warbler, Alice Lee as Ye Eun, and Yvette Nicole Brown as Pepper Lemon.
- Died During Production: Will Ryan, who played Willie the Giant, lost his battle with cancer on November 19, 2021.
- The Original Darrin:
- After being replaced by Daniel Ross for Mickey Mouse Roadster Racers & Mixed-Up Adventures, Tony Anselmo returns to voice Donald again presumably due to Legend of the Three Caballeros, Kingdom Hearts III, and DuckTales (which were all in production when Roadster Racers started) all wrapping up by the time this series began production and freeing up Anselmo's schedule.
- After being replaced by Jaime Camil on Legend of the Three Caballeros and Arturo del Puerto on DuckTales, Carlos Alazraqui returns to voice Panchito Pistoles.
- The Other Darrin:
- Due to Tress MacNeille being too busy with other projects, her roles were recast in seasons 2 and 3 with Debra Wilson as Daisy and Jan Johns as Chip.
- After Will Ryan died in 2021, Brock Powell succeeded him as Willie starting in "Tooth or Consequences!".
- Due to Rob Paulsen stepping down from the role in 2020 due to the recent trend of recasting characters of color, Sérgio Stern takes over as José Carioca in this series, having already provided the character's voice in Brazilian Portuguese as well as in theme parks. He also by extension replaces Eric Bauza from Legend of the Three Caballeros and Bernardo de Paula from DuckTales.
- Posthumous Credit: Will Ryan reprised his role as Willie the Giant in several episodes aired after his death on November 19, 2021.
- Role Reprise: The following return to their roles:
- Bret Iwan as Mickey
- Kaitlyn Robrock as Minnie
- Bill Farmer as Goofy, Pluto, Horace, and Mayor McBeagle
- Tress MacNeille as Daisy and Chip in season 1
- Corey Burton as Dale and Von Drake
- Tony Anselmo as Donald as mentioned on the above The Original Darrin section
- Jim Cummings as Pete
- April Winchell as Clarabelle and Hilda
- Nika Futterman as Cuckoo Loca
- Will Ryan as Willie the Giant in season 1 and one season 2 episode until his passing
- Maurice LaMarche as Mortimer Mouse
- Carlos Alazraqui as Panchito Pistoles as mentioned on the above The Original Darrin section
- Roz Ryan as Thalia
- Lillias White as Calliope
- You Sound Familiar: Daniel Ross, who voiced Donald back in Roadster Racers/Mixed-Up Adventures, voices Martian Mickey and Martian Minnie's pet Zoop Bloop here.
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