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Nanoparticles of sulfonamide are prepared by the reaction of a benzenesulfonyl chloride with ammonia or an amine in acetonitrile solvent. The ultrasonic treatment was applied for preparation of nanoparticles. The produced sulfonamide nanoparticles were characterized by X-ray diffraction (XRD), infrared spectroscopy (IR), transmission electron microscope (TEM), scanning electron microscope (SEM), and other techniques. The antibacterial activities of sulfonamide nanoparticles derivatives tested against microorganism and compared with bulk forms (non-nano) conditions. The antibacterial activities of synthesized compounds were studied against two Gram-negative bacteria, Escherichia coli, Klebsiella pneumoniae, and two Gram-positive species, Staphylococcus aureus and Bacillus subtilis. These compounds antifungal activities have been studied against, Candida albicans, Aspergillus flavus, Aspergillus nigar.