Main Hoon Na tells the story of Major Ram Prasad Sharma (Shahrukh Khan) and his efforts to foil the terrorist Raghavan (Sunil Shetty). Major Sharma is simultaneously attempting to mend relations with his father's estranged first wife and his half-brother Lakshman; complications ensue.

Raghavan is a former military officer dismissed for executing Pakistani civilians. He wants to sabotage a military project called Milaap (Unity), a first step towards friendship between India and Pakistan. India will release fifty Pakistanis imprisoned for crossing the border into India -- most of them illiterate villagers who wandered over the border by mistake. Raghavan does not want the state of war between India and Pakistan to end; he lost his son in the Indo-Pak wars in Kashmir and cherishes an abiding hatred for Pakistan and all Pakistanis.

First he tries to stop Project Milaap by killing the general in charge, General Bakshi (Kabir Bedi) during a national television interview. This fails, though he does succeed in killing Brigadier Sharma (Naseeruddin Shah), Major Sharma's (Ram's) father.

As the father dies, he tells Ram about his stepmother (Kiron Kher) and half-brother Lakshman (Zayed Khan) and begs Ram to re-establish relations with them, who are to be found at a college town in the Himalayas (Darjeeling). Both brothers should cast their father's ashes into the Ganges.

Raghavan again tries to stop Project Milaap, this time by threatening to kill General Bakshi's daughter Sanjana (Amrita Rao). The General asks Major Ram Sharma to protect Sanjana; Ram pleads that he has family responsibilities. The General points out that, by a strange coincidence, Sanjana attends school in the same town where Lakshman lives, so Ram can protect Sanjana and look for Lakshman at the same time. Ram must go under cover, as Sanjana is estranged from her father and will not accept any military escort.

So Ram pretends to be a college student, returning to college after many years away. He is much older than the other students, who at first make fun of him because of his lack of new-generation styles. He soon proves his worth and becomes a big man on campus.

He finds Lakshman or (later revealed to be his brother), who has failed term thrice, befriends Sanjana, and succeeds in foiling Raghavan. Ram falls in love with chemistry teacher, Chandani (Sushmita Sen) and Lucky falls in love with Sanjana.

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