Shanthi Krishna started off in the Malayalam film industry as a well-known dancer and debuted in the industry with the film Salini Ente Kootukari in 1980. Her debut in the acting sphere of Malayalam film industry started with Nidra (1981). She also did a Tamil film Paneer Pushpangal in the same year. She quit the film industry after her first marriage but made a comeback in 1991 with the film Nayam Vyakthamakkunnu. She was also the recipient of the Kerala State Film Award for Best Actress for Chakoram (1994). The year 1997 saw her complete withdrawal from the Malayalam film industry. However, she made a second comeback in 2017 with the movie Njandukalude Nattil Oridavela before working in Aravindante Athidhikal.

In 2018, she appeared alongside Kunchacko Boban and Nimisha Sajayan in Soumya Sadanandan's Malayalam comedy drama Mangalyam Thanthunanena.