Reni Santoni:
voice of one of the rats has a cameo as a human, playing the circus owner talking to the cops after Dolittle takes Tiger for surgery. He is wearing a white long haired wig.
Both Albert Brooks and Ellen Degeneres have voice-overs in the movie (Albert plays the tiger and Ellen plays the dog at the beginning of the movie). They would later star together in the Pixar film Finding Nemo, doing the voices of Marlin and Dory.
When John and Rodney are in the car, after Rodney says, "Okay, let's chill. Let's just chill," the scene switches to John getting out of the car. You can see that Rodney has shifted to a different guinea pig.
When Gene and Mark are walking downstairs to check out Mark's nose after it has been broken, Mark is wearing a wedding ring. However, in the next shot when they find John in the room, the wedding ring is no longer on Mark's finger.
Archer Dolittle: [to Lisa and Maya, the latter of whom has resolved to give up her experiments and be more like John]
... John's always been able to talk with animals. I used to think it was a handicap, but it's not; it's a gift. Sometimes, daddies are the ones who need to change.
Reverend: Leave this boy, devil man! Go now, Satan, take the serpent's voices with ya! I command you to come out of this boy! Come on out of this boy! God said it! Come on out of this boy!