The film opens with a historical story in which the goddess Parvathi while performing dance with her husband Lord Shiva drops her nose stud (Mookuththi in Tamil) on the Earth and because of which a temple was raised named "Mookuththi Amman temple" in Tamil Nadu. The nose stud has many powers in it and so an evil powered soul named "Kaalabhairavan" / "Kalabhairav" (Prakash Raj) waits one thousand years patiently to capture it.

John McKenzie (Bentley Mitchum), an American student from Pittsburgh comes to India to visit and research the Mookuththi Amman temple and stays in his Indian friend Vasu's home. He is received warmly by his friend's family. John visits the temple and he learns the Mookuththi history by the temple key person Swami Paramananda aka Swamiji (Anupam Kher) and a leaf which guides them to protect Mookuthi from evil powers which is visible only to him and not to John. John does not believe the story yet he believes only whatever he sees in his own eyes. Meanwhile, John develops a love for Vasu's sister Vani (Jyothika) which is disliked by Vasu's parents. Kalabhairavan wakes up from his long patience and captures the Mookuththi by one of his faithful servants by hypnotizing him. But the Mookuththi does not allow itself to go out of the temple and hides in a snake hill inside the temple. John is charged for the theft of Mookuththi and arrested by police despite Swamiji's repeated words that he did not steal it. John escapes from police custody and seeks the help of Swamiji. Swamiji throws powder on him with an intention of making him invisible but John turns to a small tiny little being.

Swamiji was arrested with the charge of concealing someone charged with a crime. John seeks Vani's help and they go to the police station with John in her pocket. Swamiji instructs him that the Mookuththi should be placed back in Amman's nose by that day's sunset else John will be 'Little John' forever. John takes away the Mookuththi from snake hill. Meanwhile, Kalabhairavan attempts to capture the Mookuththi. After several struggles between evil and divine, Mookuthithi is placed back in Amman's nose by John which destroys the evil Kalabhairavan. John gets back to his normal size and unites with Vani.