A series of 2,6-disubstituted and 2,5,6-trisubstituted imidazo[2,1- b][1,3,4]thiadiazoles were synthesized, the structures of the compounds were elucidated and screened for antitubercular activity against Mycobacterium tuberculosis H 37Rv using the BACTEC 460 radiometric system, antibacterial activity against Escherichia coli and Bacillus cirrhosis, and antifungal activity against Aspergillus niger and Penicillium wortmanni. Among the tested compounds 2-(2-furyl)-6-phenylimidazo[2,1- b][1,3,4] thiadiazole-5-carbaldehyde ( 6c) and (2-cyclohexyl-6-phenylimidazo[2,1- b][1,3,4]thiadiazol-5-yl)methanol ( 7a) have shown the highest (100%) inhibitory activity. Compounds 6a, 6b, 7c, and 8a exhibited moderate antitubercular activity with percentage inhibition 36, 30, 15, and 20, respectively, at a MIC of >6.25 μg/ml.