| Cast list | | Chris Rock | as | Osmosis Jones (voice) | | Laurence Fishburne | as | Thrax (voice) | | David Hyde Pierce | as | Drix (voice) | | Brandy Norwood | as | Leah (voice) | | William Shatner | as | Mayor Phlegmming (voice) | | Ron Howard | as | Tom Colonic (voice) | | Kid Rock | as | Kidney Rock (voice) | | Kenny Olson | as | Kidney Rock (voice) | | Jason Krause | as | Kidney Rock (voice) | | Joe C. | as | Kidney Rock (voice) | | Stefanie Eulinberg | as | Kidney Rock (voice) | | Jimmie Bones | as | Kidney Rock (voice) | | Uncle Kracker | as | Kidney Rock (voice) | | Jonathan Adams | as | Additional Character Voice (voice) | | Carlos Alazraqui | as | Additional Character Voice (voice) |
| | Crew list: | | Bobby Farrelly (Director) | | Peter Farrelly (Director) | | Marc Hyman (Writer) |
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