– Michelle Yeoh as Evelyn Quan Wang, a dissatisfied and overwhelmed laundromat owner; and as several other versions of Evelyn in alternate universes.
– Stephanie Hsu as Joy Wang, Evelyn's daughter; and Jobu Tupaki, Alpha-Evelyn's omnicidal daughter whose growing nihilism is a threat to the entire multiverse.
– Ke Huy Quan as Waymond Wang, Evelyn's meek and goofy husband whose existentialism is the antidote to Jobu's nihilism; and as Alpha-Waymond, from the Alphaverse; and other versions of Waymond in alternate universes
– Jenny Slate as Debbie the Dog Mom, a laundromat customer. Her original name of Big Nose was changed for the film's digital release because of its association with Jewish stereotypes.
– Harry Shum Jr. as Chad, a teppanyaki chef working alongside an alternative Evelyn in another universe.
– James Hong as Gong Gong (Cantonese for 'grandfather'), Evelyn's demanding father; and Alpha-Gong Gong, Alpha-Evelyn's father in the Alphaverse who wants Evelyn to sacrifice Joy to impede Jobu.
Jamie Lee Curtis as Deirdre Beaubeirdre, an IRS inspector; and as several other versions of Deirdre in alternate universes.