Simran made her debut in the 1995 Hindi  film Sanam Harjai  directed by Saawan Kumar. Jaya Bachchan offered her a leading role in Tere Mere Sapne. She then starred in supporting roles in Muqaddar, Angaara, Daadagiri, Bal Bramhachari, Agni Morcha, Gunda Gardi. Simran also starred in Anari No.1.

Simran then moved to south Indian movies by acting first in a high budget Malayalam film, Indraprastham. Simran was later introduced in Tamil movie Nerruku Ner by Vasanth.

Simran starred in several movies such as V.I.P, Natpukkaga, Aval Varuvala and Kannedhirey Thondrinal. Simran appeared in the movie Thulladha Manamum Thullum for which she won the Tamil Nadu State Film Award for Best Actress.

Simran's act in the movie Vaali, alongside Ajith won several awards for her acting, including a Tamil Nadu government award and a Kalaimaamani award and she was nominated for National Film Award for Best Actress.

Simran has also worked in movies like Priyamaanavale and Parthen Rasithen in which she acted in a negative role and won a Tamil Nadu government award.

Simran has appeared in Ramana, Pammal K. Sambandam, Panchathantiram , Thamizh, and Mani Ratnam’s Kannathil Muthamittal, for which she won several accolades for her performance, including a Filmfare award, a ITFA Best Actress Award and a “Dinakaran Best Actress Award”.

Simran left the Tamil industry after her Marriage with her last movie New for which she became the highest paid south Indian actress by getting 75 lakhs.

After her marriage, Simran made a comeback with Gautham Vasudev Menon's Vaaranam Aayiram alogside Surya, for which she won the Filmfare Best Supporting Actress Award. Simran then worked in negative roles in Seval, Aiyantham Padai and in s supporting role in TN-07 AL 4777, alongside Pasupathy.

Simran's work in Telugu movie industry started with debut in Abbai Gari Pelli in 1997. Later, Simran starred in Samarasimha Reddy and in Kalisundam Raa and Nuvvu Vastavani. Simran also starred in Yuvaraju and Goppindi Alludu.Simran ahs also acted in movies like Mrigaraju, Bava Nachadu and Daddy as well as Narasimha Naidu. In 2002 Simran starred in Seema Simham. Simran made a comeback in Telugu after marriage, with Okka Magadu in 2008 which was followed by John Appa Rao 40 plus.