Small-leaved Kuding tea is a traditional Chinese tea that is rich in polyphenols. In the current study, we investigated the preventive effect of small-leaved Kuding tea (SLKDT) on D-galactose-induced oxidative aging in mice. Changes in serum, skin, liver, and spleen of experimental animals were determined using biochemical and molecular biology techniques. Biochemical analysis demonstrated that polyphenol extract of SLKDT (PSLKDT) improved the indices of the thymus, brain, heart, liver, spleen, and kidney function in model mice. PSLKDT prevented a decrease in the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) as well as an increase in nitric oxide (NO) and malondialdehyde (MDA) levels in serum, liver, and spleen. Pathological assessment also showed that PSLKDT reduced oxidative damage induced by D-galactose in skin, liver, and spleen. We further found that PSLKDT upregulated neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), Cu/Zn-SOD, Mn-SOD, catalase (CAT), heme oxygenase-1 (HO-1), nuclear factor (nuclear factor-erythroid 2 related factor 2 (Nrf2), γ-glutamylcysteine synthetase (γ-GCS), and NAD(P)H dehydrogenase [quinone] 1 (NQO1) mRNA expression and downregulated inducible nitric oxide synthase (iNOS) mRNA expression. Protein levels of SOD1 (Cu/Zn-SOD), SOD2 (Mn-SOD), CAT, GSH1 (γ-glutamate-cysteine ligase), and GSH2 (glutathione synthetase) in the liver and spleen were also increased by PSLKDT treatment. Collectively, these results indicate that PSLKDT is effective in preventing D-galactose-induced oxidative aging in mice, and its efficacy is significantly higher than antioxidant vitamin C. Because PSLKDT is a potent antioxidant and antiaging polyphenol, Kuding tea rich in PSLKDT should be considered an ideal drink with antioxidative and antiaging effects.