A series of biologically active N-(3-chloro-2 oxo-4-phenylazetidin-1-yl)/3-N-(4-oxo-2-arylthiazolidin-3 yl)-2-(methylsulfonamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamides derivatives have been synthesised in good yield. The structures of compounds have been established on the basis of IR, 1 H, 13C NMR, and elemental analysis. The structure–activity relationships have been studied by screening of antimicrobial activity over a representative panel of bacterial and fungal strains using twofold serial dilution method. All these synthesised compounds exhibited significant activities against all bacterial and fungal strains.