Two novel series of 4-thiazolidinone derivatives, bearing 2-nitrophenyl imino and 4-nitrophenyl imino groups at position-2 and substituted arylidene groups at position-5, have been synthesized and evaluated for antimicrobial activity against four bacterial and one fungal strain. The success of the synthesis of compounds was confirmed on the basis of spectral analysis. All the newly synthesized compounds were obtained in high yields and exhibited good antibacterial activity; however, the antifungal potential was limited to a few agents.