The real-life American Museum of Natural History had 20% more visitors during the holiday season following this movie's opening.
Ben Stiller and Owen Wilson were only on-set together for one day. Stiller talked to a toothpick for the Jedediah scenes. Wilson filmed all of his parts three months later.
Owen Wilson's role as Jedediah was supposed to be a cameo (which is why he's uncredited). His character tested so well with the audience, they expanded the role.
(at around 1h 17 mins) When the night guards chase Nick up the stairs, only Dick Van Dyke performed the stunt himself. The other two actors required younger stunt doubles.
Ricky Gervais: [sentence] Dr. McPhee rarely finishes his sentences. E.g., when Larry is getting his job back, Dr McPhee says, "Fool me once, shame on you. Fool me twice..."