Sodium valproate and tomato extract have been studied in different experimental models of epilepsy individually. The aim of the present study was to evaluate the effect of lycopene on the antiepileptic effects of sodium valproate against pentylenetetrazol-induced kindling in mice. Swiss albino mice of either sex were randomly divided into 5 groups, with each group containing 8 mice. These groups were treated with pentylenetetrazol (45 mg/kg on days 8, 10, and 12 and 70 mg/kg on day 14 day, i.p.); sodium valproate (200 mg/kg, p.o.) + pentylenetetrazol; lycopene (2 mg/kg, p.o.) + sodium valproate (200 mg/kg, p.o.) + pentylenetetrazol; and lycopene (4 mg/kg, p.o.) + sodium valproate (200 mg/kg, p.o.) + pentylenetetrazol, for 14 days, respectively. After treatment, the animals were observed for 30 minutes for behavioral analysis. Subsequently, the animals were sacrificed, and their brain was removed for the biochemical estimations of thiobarbituric acid reactive substances, catalase, superoxide dismutase activity, reduced glutathione, and gamma-aminobutyric acid. Significant pentylenetetrazol-induced seizure was characterized by alteration in the seizure score and latency as well as a significant increase in the levels of brain thiobarbituric acid reactive substances and a significant decrease in reduced glutathione, catalase, superoxide dismutase, and gamma-aminobutyric acid levels. Treatment with sodium valproate and lycopene significantly restored the seizure score, latency, thiobarbituric acid reactive substance, reduced glutathione, catalase, superoxide dismutase, and gamma-aminobutyric acid levels near to normal compared to pentylenetetrazol. The present study provides experimental evidence that a combination therapy of lycopene along with sodium valproate attenuated seizure and oxidative stress against pentylenetetrazol-induced kindling in mice.