The present study reported a green approach for sonochemical-assisted synthesis (SAS) of copper oxide nanoparticles (CuO NPs) by using the aqueous extract of the fruit of the Ficus Johannis plant. The aqueous extract was obtained using ultrasonic-assisted extraction (15 min, 45°C) and microwaveassisted extraction (15 min, 450 w). Next, the as-prepared aqueous extracts were used in a plantmediated approach to synthesize CuO NPs. The synthesized CuO NPs have been characterized via different techniques including X-ray Diffraction (XRD), scanning electron microscopy (SEM), dynamic light scattering (DLS), ultraviolet-visible absorption, photoluminescence, and Fourier-transformed infrared (FT-IR) spectroscopic techniques. As observed, a broad absorption band around 375 nm clari ed the successful synthesis of CuO NPs. From the SEM analysis, the average particle size of the prepared CuO NPs was estimated below 50 nm. Afterward, the antimicrobial, antioxidant, and antifungal properties of the aqueous plant extracts and the as-prepared CuO NPs were evaluated by different assays. These included the release of protein, nucleic acids, disk diffusion method, also minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), and time-killing assays.