AIM To explore the effect of Ginkgo biloba diterpene lactone glucamine injection on inflammation and oxidative indicators and proteins related to the phosphatidylinositol 3-kinase （PI3K）/serine-threonine protein kinase（Akt） signaling pathway in the blood of patients with post-stroke epilepsy. METHODS A total of 150 patients with post-stroke epilepsy in our hospital form May 2021 to April 2023 were randomly divided into two groups, each containing 75 cases. The control group was given sodium valproate for 3 months, and on this basis, the observation group was given Ginkgo biloba diterpene lactone glucamine injection for 2 weeks. The clinical efficacy and adverse reactions of the two groups were compared, as well as seizure number, duration, serum interleukin-1β （IL-1β）, matrix metalloproteinase-9 （MMP-9）,superoxide dismutase （SOD）, tumor necrosis factor-alpha （TNF-α）, glutathione peroxidase （GSH-Px）, malondialdehyde（MDA）, and protein expression related to PI3K/Akt signaling pathway before and after the treatment. RESULTS The total clinical effective rate of the observation group was 92%, which was higher than 72% of the control group （P<0.05）. After 3 months of treatment, the number of seizures and seizure duration in the observation group were less than those in the control group （P<0.05）. After 2 weeks and 3 months of treatment, the levels of IL-1β, MMP-9, MDA, TNF-α, and the expression of PI3K and Akt proteins in the observation group were lower than those in the control group, while the activities of SOD and GSH-Px were higher than those in the control group （P<0.05）. There was no significant difference in the incidence of adverse reactions between the two groups （P>0.05）. CONCLUSION Ginkgo biloba diterpene lactone glucamine injection can reduce the inflammatory level and oxidative stress response in patients with epilepsy after stroke, and regulate the PI3K/Akt signaling pathway, thereby effectively controlling seizures, with significant effects.