Abstract Objective: The study aimed to evaluate the protective effects of resveratrol (RES) against methotrexate (MTX)-induced ovarian damage in female rats and were divided into 7 groups: Material and Methods: Control; MTX (15mg/kg-1st day); MTX (1st and 3rd day); MTX (1st, 3rd and 5th day); MTX (1st day) + RES (20mg/kg); MTX (1st and 3rd day) + RES; MTX (1st, 3rd and 5th day) + RES. Since there was only one animal left in groups 4 and 6 and no animals in group 7, these groups were excluded from the evaluation. Ovarian damage was evaluated by performing hematoxylin-eosin (H-E) and TUNEL staining on ovarian tissues of rats. TAS and TOS activities in ovarian tissues were evaluated spectrophotometrically. In addition, DNA damage in blood was evaluated by comet assay. Results: As a result of biochemical analyzes, TOS levels increased in MTX groups, group 2 and 3, compared to the control group, while TOS level decreased significantly in group 5. On the other hand, TAS level increased significantly in group 5 compared to groups 2 and 3. H-E staining results showed that MTX-induced damage improved with RES (group 5) treatment. Maximum positive staining in TUNEL image; observed in equal amounts in groups 2 and 3, then in group 5. In addition, the comet score, which indicates DNA damage, increased significantly in groups 2 and 3, while it decreased significantly in group 5. Conclusion: In line with the results of this study, it was observed that resveratrol may provide protective effects against methotrexate-induced ovarian damage due to its antioxidant properties.