ABSTRACT: In the present study, the free radical scavenging activities (against 1,1-diphenyl-2-pierylhydrazy (DPPH), 2,2'-Azinobis-(3-ethylbenzthiazoline-6- sulphonate) (ABTS+), Hydrogen peroxide (H2O2)) of dimethylglycine sodium salt (DMG-Na) were measured and compared with those of Trolox (6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid), a commonly used antioxidant. The radical scavenging activities of DMG-Na were found to be the highest at 40 mg/ml. In Experiment 2, gastric intubation in mice with 12 mg DMG-Na/0.3 ml sterile saline solution significantly increased (P < 0.05) the body weight (BW) (28 d), organ proportion (liver and spleen), and antioxidant capacity in serum and the liver (Superoxide dismutase (SOD), Hydrogen peroxidase (CAT), Glutathione peroxidase (GPx), and Total antioxidant capacity (T-AOC)), and significantly decreased (P < 0.05) the activities of serum Glutamic-pyruvic transaminase (ALT) and Glutamic oxalacetic transaminase (AST) and Methane Dicarboxylic Aldehyde (MDA) contents in the serum and liver. Specifically, the effect of 12 mg DMG-Na/0.3 ml sterile saline solution, which showed the highest antioxidant capacity, was further studied using a mice model. In Experiment 3, the mice CL (CON+ lipopolysaccharide (LPS)) group showed a significant decrease (P < 0.05) in the serum ALT and AST content; hepatic mitochondrial antioxidant capacity (Manganese Superoxide dismutase (MnSOD), Glutathione reductase (GR), GPx, Glutathione (GSH)); MDA and Protein carbonyl (PC) content; Reactive oxygen species (ROS) level, Mitochondrial membrane potential (MMP) level, and expression of liver antioxidant genes (Nuclear factor erythroid 2-related factor 2 (Nrf2), Heme oxygenase 1 (HO-1), Manganese superoxide dismutase (MnSOD), Glutathione peroxidase 1 (Gpx1), Sirtuin 1 (Sirt1)) relative to the mice CS (CON+ sterile saline) group. The DL (DMG+LPS) group showed a significant decrease (P < 0.05) in serum ALT and AST content, ROS level, and expression of liver antioxidant gene MnSOD, Gpx1, Sirt1 and a significant increase (P < 0.05) in the hepatic mitochondrial antioxidant capacity (MnSOD, GSH, GPx, GR) and MMP level relative to the CL group. These results indicate that DMG-Na could protect against the LPS-induced oxidative stress by enhancing the free radical scavenging capacity, and increasing the activity of antioxidant defense system.