Deewane Huye Paagal begins as a sweet romance between a cute boy-next-door Karan (Shahid Kapoor) and the ravishing Tanya (Rimii Sen). The latter is the cynosure of two evil eyes because she posses the knowledge of certain secret information.

When Karan's friend coaxes him to track Tanya after she migrates to Dubai, he enlists the aid of a deceptively handsome investigator, Rocky (Akshay Kumar) to chase her down. But Rocky ends up falling in love with her at first sight. Meanwhile, Tanya's physically disabled friend, Sanju (Suniel Shetty) also has a soft corner for her and tries thwarting Rocky's attempts at getting close to Tanya.

The plot thickens when yet another unexpected party falls in love with Tanya, thus setting up a hilarious love pentagon with a gaggle of con men and a lovelorn flame-wannabe following her around like panting puppies. The funny climax, shot against the picturesque sand dunes of Dubai, is a mix of madness and mayhem!