The green synthesis of nanoparticles (NPs) offers a sustainable, rapid, and cost-effective alternative to traditional chemical and physical methods, with diverse applications across various fields. This study reports the synthesis of silver nanoparticles (AgNPs) using Ehretia rigida (Er) leaf aqueous extract and evaluates their biological activities. The formation of the NPs was confirmed by the change in colour from clear to dark brown. The synthesis parameters, such as pH, temperature, Er extract and silver nitrate (AgNO3) concentrations, reaction ratio, and incubation time, were optimized for high yields, controlled size, and stability of the NPs. The optimized Er-AgNPs were characterized using ultraviolet–visible (UV–vis) spectroscopy, dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, and high-resolution transmission electron microscopy (HR–TEM). The Er-AgNPs sample presented a characteristic absorbance peak at 408 nm, a hydrodynamic size of 74.02 ± 0.19 nm, a polydispersity index (PDI) of 0.39 ± 0.05, and a zeta potential of −25.4 ± 6.26 mV. FTIR analysis revealed the nature of the biomolecules responsible for the reduction and stabilization of the NPs. HR–TEM revealed that the Er-AgNPs were spherical, with core sizes ranging from 6 to 18 nm. The Er leaf aqueous extract and Er-AgNPs possessed antioxidant activities, with the Er leaf extract having higher activity than Er-AgNPs. The Er leaf extract did not exhibit any antimicrobial activity, whereas the Er-AgNPs demonstrated broad-spectrum antimicrobial activities against all the tested pathogens. This study provides a sustainable, easy and cost-effective method to produce AgNPs for biomedical applications.