A novel series of 11-p-substituted phenyl-12-phenyl-11a,12-dihydro-11H-indeno[2,1-c][1,5]benzothiazepines (3) has been synthesized and screened for their antimicrobial activity against Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria and fungi (Aspergillus fumigates and Candida albicans). The antimicrobial evaluation data indicated that the compounds, 3d, 3g, 3h, 3k-3p exhibited very promising antibacterial activity and the derivatives 3k, 3l, 3o and 3p exhibited high antifungal activity. The QSAR studies carried out to find out the correlation between the antimicrobial activity and physicochemical properties of synthesized benzothiazepines (3) indicated the predominance of electronic parameters in describing their antimicrobial activity.