Reproductive aging remains a primary challenge in modern medicine and biomedicine, driven by the progressive decline in oocyte quality and quantity as maternal age increases globally. This review synthesizes current knowledge at the interface of biomedicine and pharmacotherapy, focusing on cellular mechanisms and therapeutic strategies to combat oocyte senescence. The fundamental drivers of reproductive decline include mitochondrial dysfunction, impaired DNA repair pathways, and heightened oxidative stress, which collectively compromise meiotic maturation and developmental competence. A central focus of contemporary pharmacotherapy is the restoration of metabolic and epigenetic homeostasis within the oocyte. This review also evaluates emerging molecular-targeted strategies and microenvironmental interventions to optimize the follicular niche and support oocyte health. Despite the success of these interventions in various animal models, their translation into human clinical practice remains complex. Ultimately, while pharmacological strategies offer a transformative path for extending the female reproductive lifespan, a deeper understanding of the molecular triggers of oocyte aging is essential for the effective implementation of these biomedical innovations. Last but not least, ethical challenges concerning oocyte rejuvenation will be elucidated.