Several 3-[5-(4-substituted)phenyl-1,3,4-oxadiazole-2-yl]-2-styryl quinazoline-4(3H)-one were synthesized and screened for antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli and antifungal activity against Aspergillus niger and Fusarium oxysporum by the serial dilution technique. Compounds were prepared by reacting corresponding 2-methtyl quinazolinone and 4-subustituted benzaldehydes in glacial acetic acid. Physicochemical and spectral data were consistent with newly synthesized compounds. The prepared compounds were compared with previously synthesized 2-methyl-3-[5-(4-substituted)phenyl-1,3,4-oxadiazole-2-yl]-quinazoline-4(3H)-ones for antimicrobial activity. The present study revealed that styryl moiety at the second position of 4(3H) quinazolinone marginally increased the biological activity and exhibited better antibacterial than antifungal activities.