Abstract: Ionizing radiation triggers cellular senescence through multiple pathways, including the induction of DNA damage, oxidative stress, telomere dysfunction, and mitochondrial homeostasis imbalance, leading to pathological accumulation of the senescence-associated secretory phenotype (SASP). This consequently gives rise to long-term radiotherapy complications such as tissue fibrosis, immunosuppression, and secondary tumors. Anti-aging strategies targeting senescent cells and SASP, including senolytics, senomorphics, and metabolic modulators, have shown potential in mitigating radiation-induced complications. Currently, anti-aging interventions such as senolytics, SASP inhibitors, and metabolic modulators have achieved significant progress in delaying aging-related diseases, with mechanisms involving clearance of senescent cells, inhibition of SASP signaling, and restoration of cellular homeostasis. However, these strategies still face key challenges such as insufficient targeting specificity and organ heterogeneity in clinical translation. This review systematically summarizes the molecular mechanisms of radiation-induced senescence and recent advances in anti-aging drug development, aiming to provide insights for optimizing radiotherapy protocols and advancing precision anti-aging therapies.