Eight different 2,5-disubstituted 1,3,4-thiadiazoles have been prepared by conventional and microwave irradiation (MWI) methods using different aromatic or aliphatic carboxylic acids (1) and thiosemicarbazide (2). All the compounds have been prepared, purified and characterized by their spectral (IR, 1H NMR and Mass) data. The methods employed have been compared in terms of yields, reaction times. All the experimental conditions in MWI method, when compared to conventional, are easy, simple, eco-friendly and the reactions are rapid and high yield. All the compounds have been evaluated for their antimicrobial activity against Staphylococcus aureus. Escherichia coli, and Pseudomonas aeugenosa. Compounds showed mild to moderate activity, but not comparable with the standard (Oflaxacin).