EphB2 affects neuronal cells by altering the dendritic spines. The present study analyzed the neu-roprotective effects of gastrodine by measuring EphB2 expression in rat neural cells cultured in vitro and injured by kainic acid. Gastrodine (12.5, 25, and 50 mg/L) improved morphology in kainic acid-injured neurons, reduced lactate dehydrogenase leakage, decreased neuronal apoptosis, and increased EphB2 expression in neuronal cells. A moderate dose of 25 mg/L gastrodine resulted in the most significant effects. These results suggested that gastrodine suppressed the neurotoxic effects of excitatory amino acids and provided neuroprotection by remodeling neuronal dendritic spines. EphB2 affects neuronal cells by altering the dendritic spines. The present study analyzed the neu-roprotective effects of gastrodine by measuring EphB2 expression in rat neural cells cultured in vitro and injured by kainic acid. Gastrodine (12.5, 25, and 50 mg / L) improved morphology in kainic acid-injured neurons, reduced lactate dehydrogenase leakage, decreased neuronal apoptosis, and increased EphB2 expression in neuronal cells. A moderate dose of 25 mg / L gastrodine resulted in the most significant effects. These results suggest that gastrodine suppressed the neurotoxic effects of excitatory amino acids and provided neuroprotection by remodeling neuronal dendritic spines.