This comprehensive review explores the intricate relationship between oxidative stress and hearing loss, emphasizing its role in various types of hearing impairment, including age-related, noise-induced, and ototoxic hearing loss. The cochlea's unique anatomical and physiological characteristics, such as high metabolic activity and limited blood supply, make it particularly susceptible to oxidative damage. The review highlights the protective mechanisms of the auditory system's antioxidant defenses, including enzymes like glutathione peroxidase, catalase, and superoxide dismutase, and small-molecule antioxidants like glutathione, vitamins C and E, and coenzyme Q10. The mechanisms underlying oxidative stress-induced hearing loss are discussed, including inflammation, ischemia-reperfusion injury, hair cell death, and mitochondrial dysfunction. Preclinical and clinical studies have shown promising results for antioxidant therapies, such as dietary antioxidants, pharmaceutical drugs, gene therapy, and targeted delivery systems. These interventions have demonstrated potential in preventing and mitigating hearing loss caused by oxidative stress. The review also addresses the challenges and limitations of current treatments, such as the blood–labyrinth barrier's impact on drug bioavailability and the need for long-term safety data. Future directions include the development of regenerative therapies, personalized treatment strategies, and the integration of machine learning and big data analytics to optimize therapeutic approaches. In conclusion, the review underscores the significance of oxidative stress in hearing loss and the potential of antioxidant-based interventions to prevent and treat this condition. It emphasizes the need for further research to overcome existing challenges and to develop comprehensive, integrative strategies for managing hearing loss.This comprehensive review explores the intricate relationship between oxidative stress and hearing loss, emphasizing its role in various types of hearing impairment, including age-related, noise-induced, and ototoxic hearing loss. The cochlea's unique anatomical and physiological characteristics, such as high metabolic activity and limited blood supply, make it particularly susceptible to oxidative damage. The review highlights the protective mechanisms of the auditory system's antioxidant defenses, including enzymes like glutathione peroxidase, catalase, and superoxide dismutase, and small-molecule antioxidants like glutathione, vitamins C and E, and coenzyme Q10. The mechanisms underlying oxidative stress-induced hearing loss are discussed, including inflammation, ischemia-reperfusion injury, hair cell death, and mitochondrial dysfunction. Preclinical and clinical studies have shown promising results for antioxidant therapies, such as dietary antioxidants, pharmaceutical drugs, gene therapy, and targeted delivery systems. These interventions have demonstrated potential in preventing and mitigating hearing loss caused by oxidative stress. The review also addresses the challenges and limitations of current treatments, such as the blood–labyrinth barrier's impact on drug bioavailability and the need for long-term safety data. Future directions include the development of regenerative therapies, personalized treatment strategies, and the integration of machine learning and big data analytics to optimize therapeutic approaches. In conclusion, the review underscores the significance of oxidative stress in hearing loss and the potential of antioxidant-based interventions to prevent and treat this condition. It emphasizes the need for further research to overcome existing challenges and to develop comprehensive, integrative strategies for managing hearing loss.