A total of 17 new N-substituted derivatives (2b, 2c, 2d, 2e, 2f, 2g, 2h, 2i, 2j, 2k and 3b, 3c, 3d, 3e, 3f, 3g, 3h) of 5-((2-phenylthiazol-4-yl)methylene) thiazolidine-2,4-dione (2a) and 5-(2,6-dichloro- benzylidene)thiazolidine-2,4-dione (3a) were synthesized. The structural elucidation of the newly synthesized compounds was based on elemental analysis and spectroscopic data (MS, 1H NMR, 13C NMR), and their antimicrobial activities were assessed in vitro against several strains of Gram-positive and Gram-negative bacteria and one fungal strain (Candida albicans) as growth inhibition diameter. Some of them showed modest to good antibacterial activity against Gram-negative Escherichia coli and Salmonella typhimurium and Gram-positive Staphylococcus aureus, Bacillus cereus, and Enterococcus fecalis bacterial strains, whereas almost all the compounds were inactive against Listeria monocytogenes. All of the synthesized compounds showed moderate to very good activity against C. albicans.