Background: As a special medicinal plant in Xinjiang province, Elaeagnus angustifolia L. plays an important role in windbreak and sand fixation. Its leaves are widely used in the field of traditional Chinese medicine treatment, mainly including diarrhea, dysentery, coronary heart disease and arrhythmia. Objective: In this study, our primary goal was to understand the mechanism of action of Elaeagnus angustifolia L. leaves (EALs) in protecting Rat Schwann cells (RSC-96) against H2O2-induced oxidative stress. Materials and Methods: The study material, EALs, was collected from Xinjiang Province in China. RSC-96 cells were stimulated by H2O2. Cell Counting Kit-8 assay was used in the detection of cell viability, and the cellular apoptosis and reactive oxygen species (ROS) levels were assessed by flow cytometry. The level of nerve growth factor (NGF) was assayed through enzyme-linked immunosorbent assay, and the expression of p-Akt BAX, PI3K, Bcl-2, and Akt was analyzed by Western blot. In addition, we detected the expression level of NGF. Results: According to our results, its levels were increased after stimulation with H2O2, but the levels of ROS and apoptosis were found to be reduced. Simultaneously, after induction with H2O2, the expression of Bcl-2, PI3K, p-Akt, and Akt was increased due to the presence of EALs extract, but the expression level of BAX was reduced. According to our results, EALs protects RSC-96 cells from hydrogen peroxide stress and its antiapoptotic and antioxidant effects are mainly mediated through PI3K/Akt signaling pathway. Conclusion: EALs extracts protected RSC-96 cells against H2O2-induced oxidative stress by exerting antioxidative and antiapoptotic effects through PI3K/Akt signaling pathways.