Thyroid cancer is the most common endocrine cancer, and its prevalence has been increasing for decades. Approx. 95% of differentiated thyroid carcinomas are treated using131iodine (131I), a radionuclide with a half-life of 8 days, to achieve optimal thyroid residual ablation following thyroidectomy. However, while131I is highly enriched in eliminating thyroid tissue, it can also retain and damage other body parts (salivary glands, liver, etc.) without selectivity, and even trigger salivary gland dysfunction, secondary cancer, and other side effects. A significant amount of data suggests that the primary mechanism for these side effects is the excessive production of reactive oxygen species, causing a severe imbalance of oxidant/antioxidant in the cellular components, resulting in secondary DNA damage and abnormal vascular permeability. Antioxidants are substances that are capable of binding free radicals and reducing or preventing the oxidation of the substrate in a significant way. These compounds can help prevent damage caused by free radicals, which can attack lipids, protein amino acids, polyunsaturated fatty acids, and double bonds of DNA bases. Based on this, the rational utilization of the free radical scavenging function of antioxidants to maximize a reduction in131I side effects is a promising medical strategy. This review provides an overview of the side effects of131I, the mechanisms by which131I causes oxidative stress-mediated damage, and the potential of natural and synthetic antioxidants in ameliorating the side effects of131I. Finally, the disadvantages of the clinical application of antioxidants and their improving strategies are prospected. Clinicians and nursing staff can use this information to alleviate131I side effects in the future, both effectively and reasonably.