ETHNOPHARMACOLOGICAL RELEVANCE: Shilong Qingxue Granule (SQG), a traditional Chinese medicine, effectively treats the secondary neurological damage and functional deficits caused by cerebral hemorrhage, though its exact mechanism remains unclear. AIM OF THE STUDY: This study aimed to investigate the effects of SQG and its mechanisms. MATERIALS AND METHODS: we evaluated the effects of SQG and its extracts on glutamate induced nerve damage using in vivo and in vitro models. Brain water content was measured and brain tissue was stained with hematoxylin and eosin (HE) to evaluate the brain protective effect of SQG in rats. HPLC and UPLC-Q-TOF-MS were used to identify the chemical components in SQG. The model of PC12 cells induced by glutamate was established to detect intracellular Ca RESULTS: SQG alleviates brain edema and neuronal damage in glutamate induced rats by modulating mitochondrial apoptotic and MAPK signaling pathways. The SQG extract was separated by silica gel chromatographic column to obtain 20 components, and the S-18 improves PC12 survival under glutamate induced conditions by MMP, reducing ROS and Ca CONCLUSION: SQG and its extract demonstrate protective effects against glutamate induced nerve injury in vivo and in vitro, suggesting potential therapeutic benefits for neurological disorders involving glutamate excitotoxicity.