A new series of piperazine-1, 3, 4-oxadiazole deviatives were synthesized by the condensation of 1, 3, 4-thidaizole with substituted piperazine, in the presence of N, N-diisopropylethylamine. The structures were confirmed by IR, 1H NMR, 13C NMR and Mass spectroscopy. All the precursors were screened for anti-bacterial activity and the results indicate that phenyl substituted chloro (PO2) and hydroxy (PO6) functional derivatives possess better anti-bacterial activity towards to Gram-positive bacteria and gram-negative bacteria, Maximum zone of inhibition was observed in (PO2) against Bacillus subtillus (14.0 mm) and (PO6) against Pseudomonas aeruginosa (14.0 mm). Piperazine-1, 3, 4-oxadiazoles were synthesized by combining two active molecules into a new bioactive conjugate molecule. These new hybrid molecules have more potential biological activity than their parent molecules