Abstract: Anti-cancer therapy often causes premature ovarian insufficiency and infertility as the ovarian follicle reserve is extremely sensitive to chemotherapy drugs, such as cisplatin. Various fertility preservation methods have been explored for women, especially prepubertal girls undergoing radiotherapy and chemotherapy due to cancer. In recent years, mesenchymal stem cell-derived exosomes (MSC-exos) have been reported to play an important role in tissue repair and the treatment of various diseases. In the current study, we observed that human umbilical cord-derived MSC-exos (hucMSC-exos) after short-term culture improved follicular survival and development while receiving cisplatin treatment. Moreover, intravenous injection of hucMSC-exos improved ovarian function and ameliorated inflammatory environment within the ovary. The underlying mechanism of hucMSC-exos on fertility preservation was associated with the down-regulation of p53-related apoptosis and their anti-inflammatory function. Based on these findings, we propose that hucMSC-exos may be a potential approach to improve fertility in women diagnosed with cancer.