In this study, we investigated the protective actions of Vetiveria zizanioides oil (VET) against oxidative stress and apoptosis in a rat model of pentylenetetrazol (PTZ)-induced epilepsy model. Rats were divided into four groups: control (1 ml/kg saline, by gavage, 7 days + 1 ml/kg saline, i.p, single dose, 8th day), PTZ (1 ml/kg saline, by gavage, 7 days + 60 mg/kg, i.p, single dose, 8th day), PTZ + VET-200 (200 mg/kg VET, by gavage, 7 days + 60 mg/kg PTZ, i.p, single dose, 8th day), and PTZ + VET-400 (400 mg/kg VET, by gavage, 7 days + 60 mg/kg PTZ i.p, single dose, 8th day). Behavioral evaluation (Racine scale was used to classify the severity of seizures according to stages) and EEG recordings were taken. At the end of the experiment, the animals were sacrificed, and blood, hippocampus, and cerebral cortex tissues were removed for biochemical and histopathological examinations. PTZ injection increased the duration of the first epileptic spike and the total number of seizures and caused oxidative stress by increasing the total oxidant status (TOS). The treatment of PTZ induced neurodegenerative changes in the tissues such as increases of apoptosis, Bcl-2, Cyclin B1, and GABA expressions, but decreased Beta-tubulin. However, all the adverse changes of PTZ were modulated by the treatment of VET-200 and VET-400. In conclusion, these results showed that VET could ameliorate epileptic seiures, oxidative stress, and neuronal apoptosis in PTZ-induced seizures.