Background: Valproic acid (VPA) is a commonly prescribed antiepileptic drug. VPA could mediate endocrinal reproductive dysfunction on a long-term use. This study was designed to evaluate the possible protective effects of platelet rich plasma (PRP) alone and PRP in combination with folic acid (FA) in a rat model of VPA induced ovarian failure. Materials and Methods: Thirty-five adult rats were randomly divided into five equal groups and 14 female rats were used for PRP preparation as control, VPA, co-treated VPA with FA, co-treated VPA with PRP and co-treated VPA with FA and PRP groups. All treatments were administered for 90 days. The effects of PRP and/or FA against VPA were evaluated through assessment of ovarian oxidant/antioxidant biomarkers, hormonal assay of reproductive hormones, quantification of mRNA gene expression for ovarian steroidogenesis pathway-encoding genes. Histopathological examination of the ovarian tissues was implemented. Results: Revealed that VPA exposure caused ovarian failure as documented by the decreased ovarian superoxide dismutase and catalase activities, increased ovarian malondialdehyde levels, diminished serum reproductive hormones concentrations and repressed the ovarian steroidogenesis pathway-encoding genes. In addition, VPA-induced marked ovarian histopathological alterations and impaired folliculogenesis. PRP and/or FA treatment improved ovarian function after VPA exposure. Adding FA to PRP produced more ovarian estrogen receptors immunoexpression than those produced by PRP alone. While other protective effects against VPA induced ovarian failure are equal between the two agents. Conclusion: PRP exhibited a protective role against VPA-induced ovarian failure in adult rats. A combined PRP and FA therapy is superior to PRP alone to some extent.