A series of thiazolidine-2,4-dione derivatives (4a-4f) have been designed and synthesized by appropriate route and further characterized by physico-chemical, elemental (nitrogen and sulphur) and FT-IR spectral analysis. The purpose of this study was to screened these title compounds for antimicrobial activity against some selected microbial strains, Gram-positive (Staphylococcus aureus MTCC 1430, Bacillus subtilis MTCC 0441), Gram-negative (Escherichia coli MTCC 1573, Pseudomonas aeruginosa MTCC 2453) and fungal strain (Aspergillus tubingensis MTCC 2546) using agar well diffusion assay method for screening zone of inhibition and solid dilution method for minimum inhibitory concentration. The antimicrobial activity expressed as the diameter of zone of inhibition in millimeter and minimum inhibitory concentration in µg/ml. Amongst the series of synthesized compound screened, the compound (4e) 2-(4-((2,4-dioxothiazolidin-5-ylidene)methyl)phenoxy)-N-(4-bromophenyl) acetamide was found to be most active with the zone of inhibition 16.6-18.5 mm and MIC value 0.8-0.9 µg/ml against all the tested strains of microorganisms.