Synthesis of 1,3,4-oxadiazole derivatives has attracted considerable attention in view of therapeutic applications. In the presented research work, a series of novel 5-substituted-1,3,4-oxadiazole-2-thiol containing piperazinyl benzothiazole compounds by integrating piperazinyl benzothiazoles with 5-substituted-1,3,4-oxadiazole-2-thiol. All the synthesized compounds have been characterized by using elemental analysis, FT-IR, 1H NMR, 13C NMR spectroscopy and further supported by mass spectroscopy. Purity of all the compounds has been checked on thin layer chromatographic plate and HPLC technique. All the synthesized compounds were screened for their antibacterial activities against Staphylococcus aureus, Staphylococcus pyogenus, Escherichia coli and Pseudomonas aeruginosa and for antifungal activity against Candida albicans and Asperigillus niger . The biological activities of the synthesized compounds have been compared with standard drugs like Ampicillin and Greseofulvin. The compounds exhibited significant antibacterial and moderate antifungal activities. These compounds can be further exploited to get the potent lead compounds. The detailed synthesis and the antimicrobial screening of the new compounds are reported.