Hayagrriva is a gritty medical thriller following detective Arjun as he investigates a string of bizarre murders featuring animal-hybrid victims. As public panic climbs, he must track down a brilliant, mythologically obsessed psychopath using advanced surgical science to play God, while desperately trying to save his own family.

The film is a chaotic, comedic road trip that begins when a journalist disappears, sparking rumors involving "Big Brothers". Satya (Gowrav Shetty) impulsively takes a car, only for Madhu (Shwetha V) to jump in while fleeing goons. A masked man, Munna Bhai (Gilli Nata), joins them later, turning the journey into an unpredictable adventure filled with eccentric characters. The story blends comedy, light romance, and crime, ultimately concluding with a courtroom scene.