Abstract: Objective: To elucidate the material basis and mechanisms underlying the anti-aging effects of Shudi-Yu-Shanyao (SYS), a medicinal-food homologous formula. Methods: Potential SYS actives were screened by oral bioavailability (OB) and drug-likeness (DL) criteria, integrating LC–MS, TCMSP retrieval, and literature mining. Network pharmacology was used to identify the core targets/pathways and to construct a component–target–pathway network. Anti-aging efficacy was then evaluated in a D-galactose–induced aging mouse model. Cognitive performance was assessed by the Morris water maze. HE stain, biochemical assays, and molecular analyses explored underlying mechanisms. Results: Forty-five active components and 149 core targets were identified. Targets were enriched in aging-related pathways (including cancer and Alzheimer’s disease pathways) and key signaling cascades such as AMPK, p53 and necroptosis. Network topology highlighted five putative key components, they were quercetin, methyl palmitoleate, swertiamarin, palatinose and manninotriose. In vivo, SYS effectively mitigated aging phenotypes and improved cognition: compared with the model group, the medium and high-dose groups showed 225% and 200% more platform crossings; 84.34% and 119.35% longer time in the target quadrant, respectively (P<0.05, P<0.01). Renal function improved, with serum creatinine reduced by 8.45% (medium) and 4.91% (high), and blood urea nitrogen reduced by 10.39% (medium) and 3.40% (high) (P<0.0001). Antioxidant capacity increased (SOD activity, compared with the model group, up by 31.49% in serum and 25.26% in kidney), while MDA decreased (serum: 6.47±0.23 to 5.14±0.16; kidney: 18.25±0.31 to 15.15±0.34 nmol/mg prot; P<0.05, P<0.01). SYS downregulated p53, p21, γH2AX, and Bax, while upregulated Bcl-2 in renal tissue. Conclusion: SYS delays aging, with quercetin and other components likely acting via multi-target mechanisms that attenuate DNA damage, enhance antioxidant defenses, modulate Bax/Bcl-2 mediated apoptosis, and suppress overactivation of the p53 pathway. These findings provide a scientific basis for SYS as a medicinal-food homologous anti-aging intervention.