| Chris Rock | | Osmosis Jones |
| Laurence Fishburne | | Thrax |
| David Hyde Pierce | | Drix |
| Brandy Norwood | | Leah |
| William Shatner | | Mayor Phlegmming |
| Ron Howard | | Tom Colonic |
| Kid Rock | | Kidney Rock |
| Kenny Olson | | Kidney Rock |
| Jason Krause | | Kidney Rock |
| Joe C. | | Kidney Rock |
| Stefanie Eulinberg | | Kidney Rock |
| Jimmie Bones | | Kidney Rock |
| Uncle Kracker | | Kidney Rock |
| Jonathan Adams | | Additional Character Voice |
| Carlos Alazraqui | | Additional Character Voice |
| Keith Anthony | | Additional Character Voice |
| Eddie Barth | | Additional Character Voice |
| Sally Ann Brooks | | Additional Character Voice |
| Rodger Bumpass | | Additional Character Voice |
| Michael Carven | | Additional Character Voice |
| Paul Christie | | Additional Character Voice |
| Janis Dardaris | | Additional Character Voice |
| Wendy Dillon | | Additional Character Voice |
| Antonio Fargas | | Additional Character Voice |
| Eddie Frierson | | Additional Character Voice |
| Donald Fullilove | | Additional Character Voice |
| Jackie Gonneau | | Additional Character Voice |
| Shannon Gregory | | Additional Character Voice |
| Rif Hutton | | Additional Character Voice |
| Richard Steven Horvitz | | Additional Character Voice |
| Art Kimbro | | Additional Character Voice |
| Joyce Kurtz | | Additional Character Voice |
| Anne Lockhart | | Additional Character Voice |
| Sherry Lynn | | Additional Character Voice |
| Danny Mann | | Additional Character Voice |
| Mickie McGowan | | Additional Character Voice |
| John Melendez | | Additional Character Voice |
| Héctor Mercado | | Additional Character Voice |
| Paul Pape | | Additional Character Voice |
| Marilyn Pasekoff | | Additional Character Voice |