Chronic stress induces neuronal cell death, which can cause nervous system disorders including Parkinson’s disease and Alzheimer’s disease. In this study, we evaluated the neuroprotective effect of Clematis terniflora extract (CTE) against corticosterone-induced apoptosis in rat pheochromocytoma (PC12) cells, and also investigated the underlying molecular mechanisms. At concentrations of 300 and 500 µg/mL, CTE significantly decreased apoptotic cell death and mitochondrial damage induced by 200 µM corticosterone. CTE decreased the expression levels of ER stress proteins such as GRP78, GADD153, and BAD, suggesting that it downregulated ER stress evoked by corticosterone. Furthermore, our results suggested that these protective effects were mediated by upregulation of p-AKT and p-ERK1/2, which are involved in cell survival signaling. Collectively, our results indicate that CTE can attenuate neural damage caused by chronic stress.