The present study describes the chemical synthesis and pharmacological evaluation of a new series of 11 compounds of aryloctahydrobenzo[b][1,5]-diazepin-2-one in the forced-swimming test in mice. Three compounds (3e, 3f and 3h) exhibited impressive antidepressant activity, measured in terms of percentage decrease in immobility duration. The potent compounds did not show any neurotoxicity in the rotarod test, and the preliminary results are promising enough to warrant further studies around this scaffold. All the compounds were also screened for antimicrobial activity against P. aeruginosa, E. coli, S. Aureus and B. subtilis strains. Some of the compounds possessed marked antimicrobial activities comparable to that of reference drug, Ciprofloxacin.