Abstract <p>Chronic estrogen exposure exerts a protective effect against epilepsy. Glycitin, a phytoestrogen derived from soy, has demonstrated anticonvulsant properties by modulating oxidative stress in male Wistar rats. This study aims to elucidate the anticonvulsant mechanisms of glycitin by investigating its estrogenic properties through interactions with estrogen receptors (ERα, ERβ, and GPER1). Additionally, vascular endothelial growth factor (VEGF) is known to be upregulated in epilepsy as an angiogenesis factor; therefore, this investigation will also explore the interaction of glycitin with proteins that regulate the VEGF signaling pathway. Molecular docking studies assessed glycitin’s binding affinities to ERα, ERβ, GPER1, and biological targets that regulate VEGF signaling. Glycitin exhibited a binding energy of –2.2 Kcal/mol with ERα, alongside binding energy of 6.3 and –7.8 Kcal/mol with ERβ, and –6.2 and –8.9 Kcal/mol with GPER1. Additionally, the molecular docking results demonstrated that glycitin possesses a significant binding efficiency to proteins that regulate VEGF signaling. The findings support the hypothesis that glycitin acts as an estrogen agonist under conditions of estrogen deficiency, common in males, while potentially inhibiting ERβ signaling in states of elevated estrogen, which are known to exacerbate seizures. This dual mechanism indicates that glycitin may effectively regulate seizure activity by either mimicking or inhibiting estrogen effects, depending on the hormonal environment. In addition, this study revealed that glycitin can alleviate epilepsy-related by inhibiting proteins that regulate the VEGF signaling pathway. Future studies should focus on the effects of glycitin in female animal models, particularly post-ovariectomy, to ascertain its agonistic or antagonistic roles in epilepsy management.</p>