Prema Entha Madhuram Priyuralu Antha Katinam is the story of Jai (Chandrakanth Dutta) who in search of Maithili (Radhika Mehrotra) shifts his base to the US. There he meets Sara (Pallavi Dora) who falls in love with him. How the complication justifies the title of the film forms the crux of the story.

Ashwin(Sumanth Ashwin) is a college going youth who falls in love with Indu(Mishti). As time passes by, Ashwin leaves all his career goals behind and lives life with only Indu's point of view. This is also the time when he comes across Neeraja(Seerat Kapoor) who promises him to help find Indu.