The PXD has been shown to be an effective pharmaceutical treatment for epilepsy in children; however, the precise mechanism by which PXD exerts its antiepileptic effects remains to be elucidated. The objective of this study was to investigate the role of the ferroptosis pathway in the epilepsy model and to determine whether PXD interferes with this process to inhibit epileptogenesis. Behavioral changes in animals were assessed using the seven-point scoring method. The alterations in ferroptosis-related indicators were detected using H&E staining, TEM, immunofluorescence, ELISA, and WB analysis. Compared to the model group, both the sodium valproate and PXD groups demonstrated attenuated seizure severity. H&E staining indicated reduced inflammatory infiltration in the hippocampal tissues of the PXD and sodium valproate groups. TEM analysis revealed ameliorated mitochondrial swelling in these two treatment groups. Immunofluorescence showed diminished ROS levels in the PXD and sodium valproate groups. Specifically, the PXD group exhibited upregulated hippocampal expression of GSH, GPX4, HO-1, and SLC7A11, accompanied by downregulated MDA and ACSL4 expression. However, neither serum iron levels nor Nrf2 protein expression displayed significant alterations in the PXD or sodium valproate groups. In conclusion, PXD ameliorates seizure scores in PTZ-induced epileptic rat models by modulating the ferroptosis pathway.