Background: Loss of retinal ganglion cells (RGCs), which eventually leads to optic nerve atrophy and vision loss, is the main cause of glaucoma and traumatic optic neuropathy. Acteoside is the effective component of Yunnan Kudingcha, which has been reported to exert neuroprotective effects and protects RGCs from injury. However, the underlying mechanisms of acteoside in RGC injury remain largely elusive. Methods: Human RGCs was treated with hydrogen peroxide (H2O2). The expression of miR-155 and lncRNA CASC2 in RGC-5 cells was measured by RT-qPCR. The viability of RGCs was determined by the MTT assay. Flow cytometry and TUNEL staining were used to detect cell apoptosis. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were determined using ELISA kits. The mTOR and autophagic proteins were measured by western blot. Results: We identified the expression of miR-155 was upregulated in H2O2-treated RGCs, and enhanced miR-155 promoted RGC autophagy and apoptosis. Acteoside administration reduced miR-155 expression and abolished miR-155-mediated RGC injury. The expression of CASC2 was decreased in H2O2-treated RGCs. Acteoside administration could increase CASC2 expression and CASC2 overexpression reverses the effect of miR-155 overexpression on acteoside treatment-RGCs. Mechanistically, we discovered that highly expressed miR-155 promoted RGC autophagy and apoptosis via the mTOR pathway. In addition, acteoside attenuated RGC autophagy and apoptosis via the miR-155/mTOR axis. Together, these results identify a mechanism by which acteoside attenuates H2O2-induced RGC apoptosis and autophagy via the CASC2/ miR-155/mTOR axis. Conclusions: Acteoside protects RGC-5 cells against H2O2-induced cell injury via the CASC2/rniR-155/ mTOR axis. These results provide new insights for early medical interventions in patients with glaucoma.