Resveratrol-loaded liposomes significantly protected ovarian function in mice exposed to cyclophosphamide chemotherapy by activating the HIGD1A/NF-κB/SOD2 signaling pathway. The nanoformulation restored anti-Müllerian hormone levels, reduced follicle-stimulating hormone elevation, and preserved ovarian tissue architecture while enhancing mitochondrial membrane potential and reducing granulosa cell death. The protective mechanism centered on upregulating HIGD1A protein, which inhibited inflammatory NF-κB activation and boosted SOD2 antioxidant enzyme expression. This finding addresses a critical gap in fertility preservation for cancer survivors, as chemotherapy-induced ovarian damage affects millions of women globally yet lacks targeted interventions. The liposomal delivery system likely enhanced resveratrol's bioavailability and tissue penetration compared to free compound. While promising, this mouse study requires human validation and safety assessment. The research represents meaningful progress toward protecting reproductive health during cancer treatment, potentially preserving fertility options for young women facing chemotherapy. The identified HIGD1A pathway offers new therapeutic targets, though clinical translation remains years away.