Objective: This study investigates the protective effect of butylphthalide on hippocampal mitochondria in epileptic rats. Methods: (1) A rat model of pentylenetetrazol (PTZ)-kindling was used. (2) Enzymatic activity of respiratory chain complexes II and IV was quantified in the hippocampus. (3) Mitochondrial morphology of the hippocampal CA3 region was observed by transmission electron microscopy; (4) Electrical activity of the rat hippocampal CA3 region was recorded with an electrode in vivo. Results: Compared with the epilepsy (EP) group, the butylphthalide (NBP) group showed significantly improved mitochondrial respiratory chain complex IV activity in epileptic hippocampi [Control group (78.2967 +/- 7.6304) mmol Cytc/min/mg; EP group (45.3269 +/- 11.6556) mmol Cytc/min/mg; and NBP group (72.1153 +/- 15.1009) mmol Cytc/min/mg (P < 0.01). In addition, the mitochondrial ultrastructural damage was reduced and the frequency of electrical bursts in the hippocampal CA3 region decreased. Conclusion: Butylphthalide has a protective effect on mitochondrial function in the hippocampus of epileptic rats, thereby reducing the abnormal electrical activity of neurons. It may therefore have potential as an adjuvant in treatment during the active epilepsy phase.