As a continued research towards the thiadiazole derivatives, we explored here synthesis of 2-[(5-{[(Z)- phenylmethylidene/phenylethylidene]amino}-1,3,4-thiadiazol-2-yl)methyl]-1H-isoindole-1,3 (2H)-dione Derivatives (3a-3j) from 2-[(5-amino-1,3,4-thiadiazol-2-yl)methyl]-1H-isoindole-1,3(2H)-dione (2) by using different aldehyde/substituted acetophenone in glacial acetic acid by microwave irradiation. All the synthesized compounds were characterised on the basis IR, 1H NMR, 13C NMR and Mass spectral analysis, also synthesized compounds were screened for their antibacterial activity against Gram positive and Gram negative bacteria. Some of the synthesized compounds have potent activity as compared to that of the standard streptomycin.