1,3,4-oxadiazoles are interesting compounds because of their valuable biological effects such as cytotoxic, antibacterial, antifungal, and anti-tubercular activities. Ethyl mandelate was treated with hydrazine hydrate to yield the corresponding acylhydrazide. Some of the 2,5 disubstituted 1,3,4-oxadiazole derivatives were prepared from acylhydrazide using three different procedures. In the first procedure, acylhydrazide was reacted with nitro or chloro aroyle chloride to afford a diacylhydrazide which was cyclized to 2,5-disubstituted 1,3,4-oxadiazole in the presence of phosphoryl chloride as dehydrating agent. In the second procedure, furan-oxadiazole derivative was directly prepared from carboxylic acid and acylhydrazide in one step. In the third procedure, acyl hydrazide was condensed with 5-nitrofuraldehyde to yield 5-nitrofuran-2-yl) methylene)-2-phenyl acetohydrazide intermediate which was cyclized to form the nitrofuran-oxadiazole derivative by acetic anhydride as dehydrating agent. The structures of these compounds have been elucidated by spectral IR and 1H-NMR analysis. All the newly synthesized compounds were screened for their antibacterial and antifungal activities. Compounds F3 and F4 showed remarkable antibacterial activities against Staphylococcus aureus and Escherichia coli bacteria.