<p>Premature ovarian insufficiency (POI) is an endocrine disorder that seriously affects the reproductive health and quality of life of women of reproductive age. At present, there is no effective treatment to restore ovarian function. In recent years, accumulating studies have demonstrated that mesenchymal stem cells-derived exosomes (MSC-EXO) can restore ovarian function and fertility in POI animals by inhibiting apoptosis of ovarian granulosa cells, inflammatory response or fibrosis, and improving vascular function. However, there are still many deficiencies in this new treatment, such as the lack of standardized production of EXO, long-term safety and efficiency issues, and low homing efficiency, which limit its clinical translation and widespread application. Therefore, further research is required to address challenges such as achieving standardized mass production and targeted delivery of EXO, as well as to fully elucidate their underlying mechanisms of action. This review comprehensively summarizes the current progress of MSC-EXO in POI treatment, covering topics including MSC-EXO extraction and identification techniques, their therapeutic mechanisms in POI, POI animal models, and the clinical application potential of MSC-EXO, aiming to provide support for advancing basic research and facilitating clinical applications in this field.</p>