Background: Estrogenic compounds from plant sources have raised growing concern regarding their potential involvement in hormone-dependent tumorigenesis. Elevated estrogen levels are associated with pathological changes, including tumor formation and fibrosis, particularly in estrogen-sensitive tissues such as the ovaries. Materials and Methods: This experimental study investigated histopathological and epigenetic alterations in ovarian tissue induced by tamoxifen and phytoestrogens under elevated estrogen conditions. Thirty healthy adult female rats were randomly divided into five groups. The control group received no treatment, while the treated groups were administered flaxseed oil (0.5 ml), corn oil (0.2 ml), or their combinations with tamoxifen (1 mg/kg) orally for six weeks. Ovarian tissues were examined histologically and analyzed for DNA methylation in the estrogen receptor alpha (ERα) promoter region. Results: Exposure to tamoxifen and phytoestrogens caused distinct histopathological and epigenetic alterations. A significant increase (P ≤ 0.01) in granulosa cell layer thickness was observed in all treated groups, while changes in theca cell layer thickness were not significant. DNA methylation of the ERα promoter region was markedly reduced compared to controls, indicating altered epigenetic regulation. Conclusion: Phytoestrogens may modulate tamoxifen activity by competing for estrogen receptor binding, leading to structural and epigenetic alterations that could contribute to tumorigenic processes in ovarian tissue. Continuous monitoring of estrogenic compound exposure is essential to assess their potential impact on reproductive health and cancer risk.