The present article deals with the synthesis and antimicrobial screening of a series of N-(5-(2-(5-(arylidene)-4-oxo-3-phenylthiazolidin-2-ylidene)hydrazinecarbonyl)-4-methylthiazol-2-yl)-4-methoxybenzamides (6a–o). The structures of these compounds have been elucidated by spectra (IR, 1 H NMR, 13C NMR, mass spectra). All the synthesized compounds were screened for in vitro antibacterial activity against Gram-positive (Staphylococcus aureus, Streptococcus pyogenes) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria. These compounds were also tested for their inhibitory action against three strains of fungi (Candida albicans, Aspergillus niger, Aspergillus clavatus). The thiazole derivatives discovered in this study may provide valuable therapeutic intervention for the treatment of microbial diseases, especially against bacterial and fungal infections.