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In the present study, green silver nanoparticles (Ag₂ONPs) were prepared from aqueous and ethanolic leaves extract of Rhamnus virgata in a facile, green, cost‐effective, and eco‐friendly way. The color changes from light brown to brownish black determined the synthesis of Ag₂ONPs_(Aq) and Ag₂ONPs_(Et). The phytofabrication of Ag₂ONPs was confirmed using various spectroscopic and microscopic techniques: energy‐dispersive X‐ray spectroscopy, dynamic light scattering, ultraviolet–visible spectroscopy, Fourier‐transform infrared, X‐ray powder diffraction, Raman, scanning electron microscopy, and transmission electron microscopy. Detailed in vitro biological activities determined significant biopotentials for Ag₂ONPs. The Ag₂ONPs_(Aq) and Ag₂ONPs_(Et) were investigated for anticancer potential against HUH‐7 (IC₅₀: 9.075 μg/ml for Ag₂O_(Aq) and 25.66 μg/ml for Ag₂O_(Et)) and HepG2 (IC₅₀: 25.18 μg …