The incidence of systemic microbial infections has increased severely due to the increase of immunocompromised hosts.In the present study, a novel series of Indole based Thiazolidinone derivatives were synthesized and evaluated for their in vitro antimicrobial activity. The entire synthesized compounds were confirmed by IR and 1HNMR spectroscopy study and all physicochemical properties. Compounds below are the most active compounds having antimicrobial activity.