Leydig cells (LCs) are primary for testosterone production and the preservation of male reproductive function; however, their activity is highly susceptible to oxidative stress (OS)–induced damage. Accumulating evidence indicates that excessive reactive oxygen species (ROS) disrupt redox homeostasis, impair mitochondrial function, and interfere with key steroidogenic processes, ultimately promoting cellular senescence in LCs. This review provides an updated synthesis of the molecular mechanisms underlying OS–induced LC dysfunction, with particular emphasis on mitochondrial impairment, DNA damage response, and major signaling pathways, including SIRT1/Nrf2, PI3K/Akt/mTOR, MAPK, and FOXO. In addition, we highlight the impact of senescence-associated secretory phenotype and inflammatory mediators on amplifying LC dysfunction and contributing to male subfertility. Emerging therapeutic strategies are also discussed, including antioxidant-based compounds, nanoformulations, and targeted pharmacological agents that modulate redox balance, inflammation, apoptosis, and steroidogenesis. Collectively, these insights deliver a mechanistic framework for emerging novel interventions directed at preserving LC function and improving male reproductive health.