Abstract: To investigate the protective effect of selenated Acanthopanax polysaccharide (Se-ASPS) against D-galactose-induced (D-gal) oxidative damage in mice. The oxidative damage model of mice was established by intrabitoneal injection of D-gal. The mice in the high, medium and low dose groups were supplemented with 200, 100 and 50 mg/kg·bw of selenated Acanthopanax polysaccharide, respectively. The mice were gavaged continuous intragastric administration for 28 days. Changes in body weight and feed intake and organ indices of mice in each group were compared, and HE staining was used to observe liver lesions in mice. Serum, heart, liver, spleen and kidney tissues were analyzed for SOD, CAT, GSH-Px, MDA, AST, ALT using the kit. Compared with the D-gal model group, both selenated Acanthopanax polysaccharide groups significantly increased the body weights of mice (P<0.05), and the selenated Acanthopanax polysaccharide high-dose group significantly increased the organ index of mice (P<0.05). HE staining revealed that selenated Acanthopanax polysaccharide could repair the damage caused by D-galactose to mouse liver tissue. The high-dose group of selenated Acanthopanax polysaccharides significantly increased the activities of SOD, GSH-Px, and CAT enzymes in serum, heart, liver, spleen, and kidney tissues of mice (P<0.05), and significantly decreased the contents of MDA, AST, and ALT (P<0.05), with the high-dose group showing the most prominent performance (P<0.01). Se-ASPS can significantly protect the organism against oxidative damage caused by D-gal.