The ovarian microenvironment plays a critical role in maintaining ovarian function and fertility, and chemotherapy can disrupt this environment, leading to ovarian damage and dysfunction. This review discusses the changes in the ovarian microenvironment during chemotherapy and highlights the importance of targeting this environment to protect ovarian function. The ovarian microenvironment includes the extracellular matrix (ECM), stromal cells and cytokines, vascular system, immune components, and ovarian stem cells. These components are essential for follicle development, ovulation, and corpus luteum formation. Chemotherapy can cause changes in the ovarian microenvironment, such as ECM deposition, vascular damage, immune imbalance, oxidative stress, and stem cell exhaustion, which can lead to reduced ovarian function and fertility. Several approaches have been proposed to protect against chemotherapy-associated ovarian damage, including stem cell therapy, free radical scavengers, immunomodulators, senolytics, and proangiogenic factors. Understanding the role of the ovarian microenvironment in chemotherapy-associated ovarian damage is essential for developing new therapeutic strategies to preserve ovarian function and fertility in cancer patients.The ovarian microenvironment plays a critical role in maintaining ovarian function and fertility, and chemotherapy can disrupt this environment, leading to ovarian damage and dysfunction. This review discusses the changes in the ovarian microenvironment during chemotherapy and highlights the importance of targeting this environment to protect ovarian function. The ovarian microenvironment includes the extracellular matrix (ECM), stromal cells and cytokines, vascular system, immune components, and ovarian stem cells. These components are essential for follicle development, ovulation, and corpus luteum formation. Chemotherapy can cause changes in the ovarian microenvironment, such as ECM deposition, vascular damage, immune imbalance, oxidative stress, and stem cell exhaustion, which can lead to reduced ovarian function and fertility. Several approaches have been proposed to protect against chemotherapy-associated ovarian damage, including stem cell therapy, free radical scavengers, immunomodulators, senolytics, and proangiogenic factors. Understanding the role of the ovarian microenvironment in chemotherapy-associated ovarian damage is essential for developing new therapeutic strategies to preserve ovarian function and fertility in cancer patients.