Tehran University of Medical Sciences Journal of Family and Reproductive Health 1735-8949 19 4 2025 12 31 265 271 Vadivelan Ramachandran Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, The Nilgiris, Tamil Nadu, India Suriya Naarayanan Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, The Nilgiris, Tamil Nadu, India Kavi Kumar Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, The Nilgiris, Tamil Nadu, India Gugan Murugan Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, The Nilgiris, Tamil Nadu, India Biswajyoti Mohanty Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, The Nilgiris, Tamil Nadu, India 2025 09 22 2025 12 30 Objective: This study aims to test how fisetin and dapagliflozin—alone and combined—affect reproductive cycles, blood markers, hormones, oxidative stress, and tissue changes in DHEA-induced PCOS rats. Materials and methods: This study used 30 female rats split into five groups of six animals each: normal controls, PCOS disease controls, fisetin treatment, dapagliflozin treatment, and combination treatment. PCOS was created by giving the rats DHEA injections under the skin for 21 days, followed by 28 days of treatment. The researchers measured body weight, reproductive cycles, organ weights, hormone levels (LH, FSH, testosterone, insulin), cholesterol profiles, oxidative stress markers (MDA, SOD), inflammation markers (TNF-α, IL-6), and examined tissue samples under a microscope. Results: PCOS induction in rats caused estrous cycle disruption (shown through vaginal cytology), weight gain, elevated LH/testosterone/insulin levels, and compromised antioxidant status. Individual fisetin and dapagliflozin treatments significantly ameliorated these abnormalities, but their combination demonstrated the most comprehensive therapeutic benefits, effectively restoring reproductive cycles, hormonal balance, and metabolic parameters while reducing oxidative damage. Conclusion: Fisetin and dapagliflozin, particularly when used together, helped reduce PCOS-related problems by fighting inflammation, protecting against cellular damage, and improving insulin function. This likely works by influencing the PI3K/AKT cellular signaling pathway. https://jfrh.tums.ac.ir/index.php/jfrh/article/view/3489 https://jfrh.tums.ac.ir/index.php/jfrh/article/download/3489/739