ObjectiveTo confirm the therapeutic efficacy of the ginkgo biloba extract EGb761® on ischemic stroke and elucidate its underlying mechanism. MethodsMale Sprague-Dawley rats were divided into three groups: sham, model, and EGb761 (ginkgo biloba extract). Ischemic stroke was then simulated in these rats via embolic middle cerebral artery occlusion surgery, with the extract administered half an hour before surgery. Neurological deficit scores, infarct volume, cerebral edema rate, and inflammatory factors served as the primary metrics for drug efficacy. Serum metabolites were analyzed using 1H-nuclear magnetic resonance to elucidate the operative mechanism. ResultsTreatment with the ginkgo biloba extract EGb761® significantly ameliorated the neurological deficit scores (P = .0343), diminished the cerebral infarct volume (P = .0001) and cerebral edema rate (P = .0030), and alleviated neuroinflammation (all P < .05) in middle cerebral artery occlusion rats. In addition, it significantly altered the concentrations of various metabolites, such as 2-hydroxybutyrate, isoleucine, isopropanol, isobutyric acid, N6-acetyllysine, glutamate, glutamine, methionine, and N,N-dimethylglycine (all P < .05). Enrichment analysis of the differential metabolites indicated that EGb761® may be involved in the regulation of amino acid metabolism, betaine metabolism, glucose-alanine cycle, Warburg effect, and urea cycle. ConclusionThe ginkgo biloba extract EGb761® demonstrates anti-ischemic stroke properties by regulating amino acids and amino acid derivatives, such as isoleucine, N6-acetyllysine, glutamate, methionine, and N,N-dimethylglycine.