 | Chris Rock als Osmosis Jones (voice) |
 | Laurence Fishburne als Thrax (voice) |
 | David Hyde Pierce als Drix (voice) |
 | Brandy Norwood als Leah (voice) |
 | Bill Murray als Frank Detorre |
 | Molly Shannon als Mrs. Boyd |
 | William Shatner als Mayor Phlegmming (voice) |
 | Ron Howard als Tom Colonic (voice) |
 | Sherry Lynn als (voice) |
 | Mickie McGowan als Additional Character Voice (voice) |
 | Chris Elliott als Bob |
 | Elena Franklin als Shane Detorre |
 | Kid Rock als Kidney Rock |
 | Uncle Kracker als Kidney Rock (voice) |
 | Carlos Alazraqui als Additional Character Voices (voice) |
 | Rodger Bumpass als Additional Character Voices (voice) |
 | Richard Steven Horvitz als Additional Character Voices (voice) |
 | Danny Mann als Additional Character Voices (voice) |
| Mickie McGowan als Additional Character Voices (voice) |
 | Jonathan Adams als Additional Character Voices (voice) |
| Bobby Farrelly | Director |
| Marc Hyman | Screenplay |
| Bobby Farrelly | Producer |
| Peter Farrelly | Producer |
| Zak Penn | Producer |
| Bradley Thomas | Producer |
| Randy Edelman | Original Music Composer |
| Mark Irwin | Director of Photography |
| Lois Freeman-Fox | Editor |
| Stephen Schaffer | Editor |
| Sam Seig | Editor |
| Peter Farrelly | Director |
| Steven Burch | Special Effects Supervisor |
| Adam Beck | Animation |
| Paul Dutton | Animation |
| Audrey Stedman | Layout |
| Karen Hamrock | Layout |
| Bob Camp | Storyboard |
| Jennifer Yuan | Layout |
| Marc S. Fischer | Co-Producer |
| Aaron Parry | Associate Producer |
| John Walker | Associate Producer |
| Arlan Jay Vetter | Art Direction |
| Chris Aguirre | Visual Development |
| Mark Andrews | Storyboard |
| Barry Caldwell | Storyboard |
| Ruben Chavez | Visual Development |
| Katherine C. Concepcion | Art Department Manager |
| Ricardo F. Delgado | Visual Development |
| Hani D. El-Masri | Visual Development |
| Jeff Etter | Visual Development |
| Steve Fonti | Storyboard |
| Darek Gogol | Visual Development |
| Daan Jippes | Storyboard |
| Kevin Johnson | Visual Development |
| Leon Delaney | Stunt Coordinator |
| John Bermudes | Special Effects |
| John Harajovic | Special Effects |
| William 'Billy Jack' Jakielaszek | Special Effects Coordinator |
| Carol Koch | Sculptor |
| Craig R. Maras | Animation |
| Jeannine Berger | Post Production Supervisor |
| Eddie Rosas | Animation |
| Bill Perkins | Layout |
| Earl A. Hibbert | Visual Effects |
| Randy Sanchez | Animation |
| James P. Alles | Layout |
| John Williamson | Animation |
| Joe Giampapa | Animation |
| Sam Chou | Animation |
| Shane Prigmore | Animation |
| Fred Cline | Visual Development |
| Ian Mah | Visual Effects Supervisor |
| Darlie Brewster | Supervising Animator |
| Rick Montgomery | Casting |
| Sydney J. Bartholomew Jr. | Production Design |
| Scott Jacobson | Set Decoration |
| Pamela Withers | Costume Design |
| Brenda McNally | Hair Department Head |
| Joe Rossi | Makeup Department Head |
| Stephan Franck | Lead Animator |
| Hal Olofsson | First Assistant Director |
| Ken Ross | Music Supervisor |
| Randy Thom | Sound Designer |
| Dennis Edwards | Producer |
| Louis Gonzales | Layout |
| Moroni Taylor | Storyboard Artist |
| Alan J. Hagge | Systems Administrators & Support |
