A series of 1,3-benzoxazole-5-sulfonamide derivatives have been synthesized via acetophenones, aldehydes and 2-sulfanyl-1,3-benzoxazole-5-sulfonamide using Fe(III)-montmorillonite (Fe(III)-mont) as catalyst. Catalyst is good Lewis acid and support to increase the yield of the final compounds. The structures of newly synthesized compounds were confirmed by FTIR, 1H NMR, 13C NMR and Mass spectroscopic methods. The antimicrobial potential of title compounds was tested against several bacterial and fungal strains. Some compounds exhibited comparable or better antimicrobial activity in comparison to the reference drugs Ciprofloxacin and Fluconozole. The selected compounds were also subjected for in silico molecular docking study.