Artemisia ordosica polysaccharides (AOP) can promote animal growth, improve intestinal morphology, regulate immunity, and enhance antioxidant capacity. To investigate the antioxidant capacity of AOP, three experiments were conducted. (1) Different concentrations of AOP (0, 50, 100, 150, 200, and 250 μg/mL) and 1 µg/mL VA on peripheral blood lymphocytes (PBLs) treated with/without lipopolysaccharides (LPS) were investigated to select the optimum concentration. The results showed that 150 μg/mL AOP had significant antioxidation activity. (2) The PBLs was randomly divided into eight treatments with six replicates, namely CON, AOP, LPS, ML385 (Nrf2 inhibitor), AOP + LPS, AOP + ML385, LPS + ML385 and LPS + ML385 + AOP. The results showed that under a normal condition or stress condition, AOP presented antioxidation activity via upregulating Nrf2/Keap1 pathway-related gene expression. (3) The PBLs was randomly divided into eight treatments with six replicates, namely CON, AOP, LPS, PDTC (NF-κB inhibitor), AOP + LPS, AOP + PDTC, LPS + PDTC and LPS + PDTC + AOP. The results showed that under a normal condition, AOP presented antioxidation activity via increasing TLR4/NF-κB pathway-related gene expression; under a stress condition, AOP alleviated oxidative damage caused by LPS via suppressing TLR4/NF-κB pathway-related gene expression.