In the present communication, we conceived a new synthetic approach for the preparation of novel thiazolyl-lactam/thiazole analogs. The reaction was started through cyclization of ketone with thiourea along with substituted aryl aldehydes to culminate imine derivatives which subsequently cyclized with thioglycolic acid/chloroacetyl chloride to produce final compounds. The structural elucidation of newly synthesized compounds was performed through elemental detections, FT-IR, 1 HNMR, and Mass spectrometric techniques. Antimicrobial studies were performed for all synthesized molecules by serial dilution method by tacking the positive (K. pneumonia, S. aureus, B. subtills) and negative (P. aeruginosa and E. coli.) bacterial strains. The in vitro antimicrobial screening results show that the compounds 2e, 3c, and 3d containing o-hydroxy, p-chloro, and p-nitro substituent respectively exhibit exceptional activity against S. aureus while compounds 2d and 3f bearing p-nitro and o-chloro substituent respectively were deemed to be the most competent against B. subtilis. Compounds 2d (p-nitro) and 2f (o-chloro) were found to be most potent against E. coli. In gram-negative bacterial strains, compounds 2c (p-chloro), 2g (4-OH,-OCH3), 3b (phydroxy), and 3e (o-hydroxy) were extremely potent against P. aeruginosa while compound 2e containing o-hydroxy group shows excellent activity against E.coli.