Four series of 56 new thiadiazepinoquinoline amines were synthesized and characterized by spectroscopic techniques (NMR, IR, and MS) and elemental analysis. All the compounds were screened for in vitro antimicrobial activity. Highest inhibitory activity (MIC of 0.03 mg/ml) was exerted by 2e against Bacillus subtilis and Streptococcus pyogenes, 2f against Escherichia coli and Streptococcus pyogenes, and 4k against only Bacillus subtilis. Only compounds 1g and 2g revealed potent antifungal activity (MIC 0.03 mg/ml) compared to the standard against Alternaria alternata. Most of the compounds exhibited better anti-bacterial activity than anti-fungal activity against the microorganisms employed in this study. These studies suggest that the thiadiazepinoquinoline scaffold may serve as a new promising template for further elaboration as anti-bacterial and anti-fungal drugs.