A series of new 5-(2,6-dichlorobenzylidene)thiazolidine-2,4-dione and 5-(4-methoxy-benzylidene)thiazolidine-2,4-dione derivatives (3a-h and 5a-h) were synthesized starting from 5-arylidene-thiazolidine-2,4-dione and ?-halo-ketones. The structural elucidation of the newly synthesized compounds was based on elemental analysis and spectroscopic data (MS, 1H-NMR, 13C-NMR). The synthesized compounds were screened for their antimicrobial activities against several pathogenic strains of Gram-positive and Gram-negative bacteria and one fungal strain (Candida albicans), assessed in vitro as growth inhibition diameters. Some of them displayed better inhibitory activities than that of the reference drug against the Gram-positive S. aureus, B. cereus, L. monocytogenes bacterial strains, and showed good antifungal activity against C. albicans, while the antibacterial activity against Gram-negative E. coli and S. typhimurium bacterial strains was moderate.