Excessive utilization of nanoparticles renders it necessary to produce safer and more secure nanoparticles while preserving their efficacy. In this study, Psidium guajava L. pulp extract-mediated silver nanoparticles (AgNPs) were synthesized, characterized, and further evaluated regarding their antioxidant potential. The green synthesized silver nanoparticles (G-AgNPs) showed a higher level of radical scavenging activity (RSA) (25.85%), hydrogen peroxide scavenging activity (34.34%), and ferric reducing power (0.28). The comparison of the control group (G1) with the various treatment groups (G2-G6) revealed that the levels of catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) were significantly different (P < 0.05). The levels of blood urea, uric acid, blood urea nitrogen (BUN), serum glutamic pyruvic transaminase (SGTP), serum creatinine, serum glutamic-oxaloacetic transaminase (SGOT), alkaline phosphatase, total bilirubin, and serum electrolytes were also evaluated. The results of clinical biochemistry also strengthened our hypothesis that G-AgNPs are less toxic than C-AgNPs. Finally, the histopathology of liver, kidney, and intestinal tissues indicated that green-synthesized AgNPs are relatively safer.