In the present work, we synthesized new sulfonamide derivatives with 1,3,4-oxadiazole moiety and tetrazole ring. The synthesized derivatives of sulfonamides were characterized through Fourier transform infrared, C-13-APT-NMR, H-1-NMR, and high-resolution liquid chromatography-mass spectrometry. The biological activities of resulting compound were also investigated and observed that the compounds reveal strong antimicrobial activity over some important bacterial strains including Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 13883, and Staphylococcus aureus ATCC 29213. The in vitro antifungal properties of synthesized compounds were also a target using Candida albicans NRRL Y-477 and Saccharomyces cerevisiae fungal strains. We have provided a useful guideline for future studies about the effect of the chemical structures of sulfonamide compounds on the biological activities. Among the target compounds, 7b, 7c, 7d, and 7e demonstrated surprisingly high antimicrobial activities than did others.