With an aim to introduce more biologically active compounds, S -substituted derivatives of 5-[1-(4-nitrophenylsulfonyl)piperidin-4-yl]-1,3,4-oxadiazole-2-thiol ( 3 ) were synthesized through four steps. In the first step, ethyl 1-(4-nitrophenylsulfonyl)piperidine-4-carboxylate ( 1 )was synthesized by reacting 4-nitrobenzenesulfonyl chloride ( a ) and ethyl isonipacotate ( b ) in basic medium. In the second step, compound 1 and hydrazine monohydrate were converted to corresponding hydrazide ( 2 ). In third step, hydrazide ( 2 ), CS 2 and KOH were refluxed in the presence of MeOH to acquire 5-(1-(4-nitrophenylsulfonyl)piperidin-4-yl)-1,3,4-oxadiazole-2-thiol ( 3 ). In the last step, alkyl/aralkylhalides ( 4a-o ) and 3 were made to react in an aprotic polar solvent to get the final compounds, 2-(substitutedthio)-5-[1-(4-nitrophenylsulfonyl)piperidin-4-yl]-1,3,4-oxadiazole ( 5a-o ). The synthesized compounds were structurally confirmed by spectroscopic techniques including 1 H NMR, EIMS and IR. Finally the synthesized compounds were screened for antibacterial activity against five bacterial strains.