Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials of quercetin against D-galactose (D-gal)-associated oxidative alterations that were induced experimentally in male Wistar rats. Forty-five rats were randomly allocated into five groups of nine rats each. The groups were a control group that was reared on a basal diet and injected subcutaneously with 120 mg D-gal dissolved in physiological saline solution (0.9% NaCl) per kg body weight daily and quercetin-treated groups that received the same basal diet and subcutaneous daily D-gal injections were supplemented orally with 25, 50, and 100 mg of quercetin per kg body weight for 42 days. Pancreatic and renal samples were subjected to histopathological, immunohistochemical, and relative mRNA expression assessments. Aging (p53,p21,IL-6, andIL-8), apoptotic (Bax,CASP-3, and caspase-3 protein), proliferative (Ki67 protein), antiapoptotic (Bcl2and Bcl2 protein), inflammatory (NF-kappa B,IL-1 beta, andTNF-alpha), antioxidant (SOD1), and functional markers (GCLCandGCLMgenes and insulin, glucagon, and podocin proteins) were determined to evaluate the oxidative alterations induced by D-gal and the protective role of quercetin. D-gal caused oxidative alterations of the pancreas and kidneys observed via upregulations of aging, apoptotic, and inflammatory markers and downregulated the antiapoptotic, proliferative, antioxidant, and functional markers. Quercetin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that quercetin supplementation is considered as a promising natural protective compound that could be used to delay the aging process and to maintain human health.