| Cast list |
| Reese Witherspoon | as | Susan Murphy /Ginormica (voice) |
| Seth Rogen | as | B.O.B. (voice) |
| Will Arnett | as | The Missing Link (voice) |
| Rainn Wilson | as | Gallaxhar (voice) |
| Hugh Laurie | as | Dr. Cockroach Ph.D. (voice) |
| Kiefer Sutherland | as | General W.R. Monger (voice) |
| Robert Cait | as | Additional Voices (voice) |
| Audrey Wasilewski | as | Additional Voices (voice) |
| Kirk Thornton | as | Additional Voices (voice) |
| Daran Norris | as | Additional Voices (voice) |
| Salli Saffioti | as | Additional Voices (voice) (as Sally Saffioti) |
| James Arnold Taylor | as | Additional Voices (voice) |
| Beverly Hynds | as | Additional Voices (voice) |
| Dave B. Mitchell | as | Additional Voices (voice) |
| David Kaye | as | Additional Voices (voice) |
