A newly recruited night security guard at the Museum of Natural History discovers that an ancient curse causes the animals and exhibits on display to come to life and wreak havoc.
Security guard Larry Daley infiltrates the Smithsonian Institution in order to rescue Jedediah and Octavius, who have been shipped to the museum by mistake.
Larry Daley and his heroic friends embark on the greatest adventure of their lives, as they travel to London to save the magic that, after dark, allows the museum's exhibits to come to life.