Problem Presbycusis, or age-related hearing loss, is characterized by gradual, progressive sensorineural hearing loss which accompanies aging with associated decreased speech recognition in noisy environments, slowed central processing of acoustic stimuli and impaired sound localization. In addition to impairing one's ability to communicate effectively, presbycusis jeopardizes one's autonomy, presents a safety concern and has been correlated with an increased incidence of clinical depression and social withdrawal. By 2025, it is estimated that approximately 25 million Americans will be affected, thus this presents a major public health concern. The purpose of this study is to evaluate the potential of antioxidant therapy, including two novel antioxidants, in the prevention of presbycusis. Methods C57BL6 mice were assigned to treatment or control groups. Treatment groups of mice were fed with a combination of two novel antioxidants, L-cysteine-glutathione mixed disulfide and ribose cysteine, as well as vitamin B12, folic acid, and ascorbic acid. Auditory brainstem response thresholds were recorded at baseline and on a monthly basis following initiation of treatment. Results Threshold shifts were observed according to the established pattern of age related loss associated with C57BL6 mice. Threshold shifts were decreased in the treatment group. Statistically significant differences (p<0.001) in threshold shifts were observed between the treatment and control groups for click stimulus and pure tones at 4, 8, 12, 16 and 32 kHz. The treatment group was found to have a smaller degree of shift in association with aging. Conclusion Combination antioxidant therapy effectively decreased threshold shifts on auditory brainstem responses within the established animal model for presbycusis. Significance Combination antioxidant therapy may prove a safe and cost-effective method of preventing presbycusis in our growing elderly population. Support American Academy of Otolaryngology – Head and Neck Surgery Foundation Resident Research Grant.