A series of 2,5,6-trisubstituted imidazo[2,1-b][1,3,4]thiadiazoles were synthesized, structures of the compounds were elucidated and evaluated for antitubercular activity against Mycobacterium tuberculosis H37Rv using microplate alamar blue assay (MABA) method, antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Vibrio cholera, and Escherichia coli by broth micro dilution assay method. Some compounds exhibited significant antibacterial and antitubercular activities. Compounds 10, 14, and 15 emerged as the most active molecules, showed significant antimicrobial activity and may serve as leads for further optimization.