To explore the protective effect of Grifola frondose polysaccharide on glutamate induced PC12 cells oxidative stress injury. The experiment was divided into a control group，a glutamate model group （glutamate 15 mmol/L），and a treatment group （Grifola frondose 25， 50， 100， 200 mg/L + glutamate 15 mmol/L）. MTT method to detect cell activity； microplate reader to detect antioxidant enzyme activity， anti-superoxide anion activity and malondialdehyde content； ROS Assay Kit to detect reactive oxygen species； flow cytometry to detect cell apoptosis rate. When the concentration of Grifola frondose polysaccharide is 100 mg/L， the cell survival rate is the highest （80.27 ± 0.82）%， the catalase activity is the highest 24.78 U/mL， the superoxide dismutase activity is the highest 21.42 U/mL， glutathione The Glutathione peroxidase activity is the best 48.62 µmol/L， the anti-superoxide anion activity is the largest 137.65 U/L， and the MDA content is the smallest 0.92 nmol/mL. When the concentration of Grifola frondose polysaccharide was 200 mg/L， the fluorescence intensity of reactive oxygen species compared with the glutamate group， the degree of reduction reached a very significant level （P<0.01）. Increased the activity of anti-superoxide anion. The the content of MDA significantly reduced. With the increase of polysaccharide concentration in Grifola frondose， the number of apoptosis decreases， which is significantly different from the model group. Conclusion Grifola frondose polysaccharide can inhibit cell apoptosis， increase antioxidant enzyme activity and the activity of anti-superoxide anion， and reduce the formation of reactive oxygen species and MDA. It has a protective effect on glutamate of injury of PC12 cell.