<p>Premature ovarian insufficiency (POI), particularly chemotherapy-induced ovarian failure (CIOF), severely compromises the reproductive and endocrine health of young women. Current fertility-preserving strategies, such as cryopreservation and hormone therapy, fail to restore endogenous ovarian function, underscoring the urgent need for regenerative solutions. Mesenchymal stem cells (MSCs) have emerged as a leading platform to address this challenge. This review synthesizes evidence on MSCs derived from diverse sources—including bone marrow, adipose tissue, umbilical cord, and menstrual blood—and evaluates their therapeutic potential. Preclinical studies consistently demonstrate that MSC transplantation restores follicular reserves and hormonal homeostasis, primarily via paracrine mechanisms. MSCs secrete growth factors and exosomes enriched with regulatory microRNAs (e.g., miR-21, miR-126) that inhibit apoptosis, promote angiogenesis, and activate pro-survival pathways such as PI3K–Akt in injured ovaries. While early clinical data are encouraging, significant translational challenges remain, including inefficient homing, source-dependent variability, and safety concerns such as tumorigenicity. Advanced approaches—such as cell-free exosome-based therapies and engineered biomaterials—are under development to enhance efficacy and safety. A concerted effort to standardize protocols, optimize delivery strategies, and conduct well-designed randomized trials is essential to establish MSC-based therapy as a clinically viable solution for oncofertility preservation.</p> Graphical Abstract <p></p>