The PI3K/AKT signaling axis is a key cellular mechanism that coordinates external signals for cell survival, proliferation, metabolism, and differentiation. In the ovary, fine-tuning of this network is critical for folliculogenesis, granulosa cell survival, steroidogenesis, corpus luteum function, and oocyte maturation. Disruption of this balance, either in the form of hypoactivity or hyperactivity, plays a central role in the pathogenesis of a wide range of ovarian diseases. Novel therapeutic approaches targeting this pathway are diverse, ranging from PI3K isoform-specific inhibitors and direct AKT inhibitors (such as afuresertib) to dual mTORC1/2 inhibitors (such as sapanisertib). Natural compounds and nanodrug delivery systems are also complementary options. On the one hand, inhibition of this pathway in hyperactive conditions has yielded promising results; On the other hand, activators such as SC79 could be used to preserve fertility in patients with premature ovarian insufficiency (POI). However, achieving ideal treatment faces obstacles such as the need for more precise isoform targeting, overcoming drug resistance, ensuring specific delivery to ovarian tissue, and identifying reliable biomarkers to predict treatment response. Ultimately, a deeper understanding of the molecular mechanisms regulating this axis will pave the way for precision medicine approaches to diagnose, prevent, and treat a wide range of ovarian disorders.