A series of novel thiazolidine-2,4-diones was synthesized and investigated for antimicrobial activity. The structures of all synthesized compounds were confirmed by means of elemental analysis, IR, 1H NMR, and LCMS. All compounds were evaluated for antimicrobial activity cup plate method against S. aureus, B. anthracis, P. aeruginosa, E. coli, C. albicans and A. niger. Compounds 2d and 2l showed significant activity against gram positive and gram negative bacteria. In case of antifungal activity, the zone of inhibition was ranging from 10 to 23 mm and the compounds 2c and 2e showed significant activity against the fungal strains as compared with fluconazole.