Girlfriend is a story about two intimate friends Tanya (Isha Koppikar) and Sapna (Amrita Arora) who have always been together since they were in college. Now they live together and each one of them is fond of the other, to that extent that if one does something, the other follows. Sapna meets Rahul (Aashish Choudhary) when Tanya is out of town for some work.
Sapna finds herself in a relationship with Rahul and by the time Tanya is back, Sapna has already fallen for Rahul and starts loving him. When Tanya learns of this relationship, she is jealous and reacts very adversely and in her jealousy and possessiveness comes out when she meets Rahul. Now Tanya goes all out to break Sapna's relationship with Rahul and her hidden agenda and desires come to light in the later part of the film.