Aim:This study aims to explore the neuroprotective effects of melatonin on radiation-induced injuries in the central nervous system (CNS). The potential of melatonin to mitigate oxidative stress, a primary contributor to radiation-induced damage, is examined alongside its antioxidant and anti-inflammatory properties. Additionally, melatonin\'s potential role in improving radiotherapy\'s therapeutic index and protecting healthy tissues while enhancing tumor radiosensitivity is evaluated.Material and Methods:The research synthesizes findings from experimental animal models, clinical trials, and in vitro studies to assess the efficacy of melatonin in mitigating oxidative stress, inflammation, and apoptosis caused by radiotherapy. A detailed review of animal model studies, including investigations of melatonin\'s impact on radiation-induced neurotoxicity, is included. Furthermore, insights from our prior research are integrated to provide a comprehensive understanding of the biochemical and histopathological mechanisms underlying melatonin\'s neuroprotective actions.Results:Melatonin demonstrated significant antioxidant and anti-inflammatory activity, reducing reactive oxygen species (ROS) levels, limiting radiation-induced apoptosis, and improving cellular defense mechanisms. In animal models, melatonin was associated with decreased neuroinflammation, improved BBB integrity, and better preservation of CNS architecture. Clinical trials, though limited in number, revealed that melatonin combined with radiotherapy improved patient survival rates reduced adverse effects, and enhanced quality of life by minimizing radiotherapy-induced complications such as inflammation and cognitive impairments.Conclusion:Melatonin shows substantial promise as an adjuvant therapy for radiotherapy, offering neuroprotection, reducing oxidative stress, and potentially improving therapeutic outcomes in neuro-oncological treatments. These findings emphasize the need for further research to optimize its clinical application, elucidate its mechanisms, and define precise dosing protocols to maximize its neuroprotective and radiosensitizing potential.