A matched library of twelve 8-substituted 2,5-dihydro-1,5-benzothiazepines was synthesized by trifluoroacetic-acid-catalyzed cyclocondensation of six 5-substituted 2-aminobenzenethiols with either a naphthyl chalcone (series A, 5a–5f) or a 2,4-dichlorophenyl chalcone (series B, 5g–5l). Isolated yields were 60–70%. Structures were supported by elemental analysis, IR, ¹H NMR and, for representative halo derivatives, isotope-pattern mass spectrometry. Antimicrobial activity was measured by agar-well diffusion against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans at 25, 50, 75 and 100 µg mL⁻¹. We performed a fresh descriptive analysis of 188 reported compound–organism–concentration observations, retaining four entries reported as not available as missing rather than converting them to zero. Activity indices were recomputed against the concentration-matched reference drugs. Compound 5j had the highest mean activity index across available cells, although one missing cell makes that ranking sensitive to missingness; among complete profiles, 5a ranked highest. At 100 µg mL⁻¹, 5c gave the largest mean inhibition zone (15.5 mm) and the strongest response against S. aureus (19 mm). All compounds displayed broadly concentration-dependent inhibition, but none matched the reference drugs across the complete panel. Matched-pair comparisons indicated that changing the aryl scaffold from naphthyl to 2,4-dichlorophenyl did not produce a uniform activity gain; the direction depended on the 8-substituent and organism. Because the thesis dataset contains single reported zone values without replicate-level dispersion, all rankings and correlations are exploratory. The results prioritize 5c, 5a, 5f and 5h for confirmatory broth microdilution, replicate testing and cytotoxicity evaluation.