The film begins with a 10-year-old boy named Lucas Nickle (Zach Tyler Eisen) being tormented by a bully and his gang. In turn, Lucas attacks an anthill with a squirt gun. This terrifies the ants. One ant, an eccentric wizard named Zoc (Nicolas Cage), tries to fight back. His girlfriend, a nurse ant named Hova (Julia Roberts), attempts to communicate with Lucas. She is almost crushed but is rescued by Zoc. The leaders of the colony decide to use a potion to shrink Lucas down to ant size. Lucas' parents, who fail to understand his problems, go to Puerto Vallarta, leaving him with his older sister and his Grandmother, who is obsessed over aliens. Meanwhile, the local exterminator, Stan Beals (Paul Giamatti), convinces Lucas to sign a contract to kill vermin.Later, Zoc and a small troop of ants pour the potion into his ear. Lucas wakes up and discovers that he is now nude and tiny. He is carried to the anthill into a world of giant caves, caterpillars and ants. Zoc insists that Lucas should be studied then eaten, but he is overruled by the Queen (Meryl Streep). She sentences Lucas to hard labor. Hova volunteers to train Lucas, much to Zoc's mortification. Hova and Lucas both learn about the differences between ants and humans. But when she forces him to forage for jelly beans with Kreela (Regina King) and her boyfriend, Fugax (Bruce Campbell) Lucas is unsuccessful. The ants are attacked by wasps. Lucas finds a discarded firecracker and uses it to destroy the attacker wasp and scare the other wasps away. This earns him the admiration of all the ants - except Zoc.Lucas is introduced to honeydew (the feces of caterpillars), and becomes sick from where it comes from. He is shown a painting which depicts the Great Ant Mother and the evil "Cloud-Breather", an exterminator. Lucas is told that the Great Ant Mother will return and shower the ants with honeydew, while the Cloud-breather will spell destruction for all of them. He and his friends go back to the house, where he tries to call the exterminator to cancel the contract but dials a pizza restaurant instead.Then Lucas' sister comes home and they are forced into hiding until dark. When Zoc finds out that Lucas put Hova in possible danger, he accuses Lucas of further treachery and tells him that he should find another wizard because there is no way that he will give Lucas the potion to turn him back again. Lucas runs away, frightened, and Hova becomes angry with Zoc. But when Lucas is eaten by a frog, Zoc frees him, starting to like him and realizing he was not so bad after all. Afterwards Zoc and Lucas discuss their differences. Zoc explains that ants work for the benefit of the colony. Lucas states that most humans work for personal gain. Zoc is confused as to how anything gets accomplished in Lucas' world.The next morning, Lucas finds the Ant Mother approaching. He discovers that the 'Ant Mother' is actually a giant balloon strapped to the top of Stan Beals' van used as a symbol for pest control. The ants enlist the aid of the wasps; at first, the wasps want to eat Lucas, but hearing that their nest is destroyed by Beals, they agree to help. During the battle with the exterminator, Lucas saves the lives of Hova and an injured wasp. Both the ants and wasps were no match against pesticide, but as he is about to exterminate the ant hill, a beetle and glowworm manage to bite Beals in the crotch. Lucas injects him with a shrinking potion. He runs away using a tricycle. Zoc then gives Lucas the enlarging potion and Lucas returns to his normal size. His parents return and tell him how much they missed him. He managed to beat the bigger bully while his former bullies become his friends, and the movie ends with him giving a bag of jelly beans to the ant colony.