A novel series of thiazolidinone derivatives namely 4-(4-dimethylamino-6-{4-[5-(4-ethylpiperazin-1-ylmethyl)-4-oxo-2-phenylthiazolidin-3-yl]-phenylamino}-[1,3,5]triazin-2-yloxy)-1-methyl-1H-quinolin-2-one have been synthesized from the key intermediate 4-[4-(4-aminophenylamino)-6-dimethylamino-[1,3,5]triazin-2-yloxy]-1-methyl-1H-quinolin-2-one (7). Condensation reaction of compound 7 with different aldehyde derivatives were performed to obtain Schiff base derivatives, which after cyclization gave thiazolidinones and finally they were reacted with N-ethylpiperazine to get target compounds. The newly synthesized compounds were evaluated for their antimicrobial activity against eight bacterial strains (Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Shigella flexneri) and four fungal strains (Aspergillus niger, Candida albicans, Aspergillus fumigatus, Aspergillus clavatus).