New azetidinone and thiazolidinone class of bioactive agents based on quinoline nucleus have been synthesized. 2-Chloroquinoline-3-carbaldehyde reacted with various substituted amine to form the corresponding Schiff base intermediates. We have derived final azetidinone and thiazolidinone analogues from Schiff bases using chloroacetyl chloride and 2-mercaptoacetic acid, respectively. The newly synthesized analogues were then examined for their antimicrobial activity against some bacterial and fungal strains as two gram -ve bacteria (Escherichia coli MTCC 739 and Pseudomonas aeruginosa MTCC 741), two gram ?ve bacteria (Staphylococcus aureus MTCC 96 and Bacillus subtilis MTCC 430), two fungal species (Aspergillus niger MTCC 282 and Candida albicans MTCC 183) as well as against Mycobacterium tuberculosis strain H37Rv to develop a novel class of bioactive agents. The results of bioassay showed that some of the newly synthesized azetidinones and thiazolidinones emerged as lead molecules with excellent MIC (mg/mL) values against mentioned microorganisms compared to standard drugs. The structure of the final analogues has been confirmed on the basis of IR, 1 H NMR, 13C NMR, and elemental analysis.