Oxidative stress (OS) plays a crucial role in the pathogenesis of neurodegenerativeÂ disease like Alzheimerâ€™s disease (AD). Glycyrrhizin (Gly) is one of the components of licoriceÂ roots possesses potent anti-oxidant, anti inflammatory and immune-modulatory properties.Â Lipopolysaccharide (LPS), which is the main constituent of the cell wall of GramnegativeÂ bacteria, causes massive oxidative damage in the brain upon systemic administration.Â The aim of this study is to investigate the neuro-protective effect of Gly against OS inducedÂ neuronal damage as a result of LPS administration. 72 mice were used; Gp I: Saline,Â Gp II: LPS, Gp III: Deprenyl (Dep) (positive control) and Gps IV, V, VI: Gly (5, 10 and 20Â mg/kg) respectively. Y-maze test and Open field test were performed to assess spatialÂ memory and to determine the motor activity in mice respectively. Lipid peroxidation (byÂ measuring thiobarbituric acid reactive species; TBARS), reduced glutathione (GSH) levels,Â and superoxide dismutase (SOD) enzyme activity were determined biochemically in brainÂ homogenates. Amyloid beta (AÎ²) deposition was evaluated using immune-histochemistry inÂ dentate gyrus of the hippocampus and the cerebral cortex. Results showed that LPS significantlyÂ increased TBARS and suppressed GSH level and SOD enzyme activity in addition toÂ altering spatial memory and motor activity. Dep and the three doses of Gly significantly inhibitedÂ OS induced AÎ² deposition and significantly improved both spatial memory and motorÂ activity. 20 mg/kg Gly was proven to produce maximum protection against LPS inducedÂ OS. Conclusively, these findings may advocate the protective effect of Gly against ADÂ through its antioxidant effect.