Introduction: Radiation therapy is a form of treatment used for various diseases, including cancer. This method stimulates cancer cells to be destroyed using high-energy radiation. The consumption of vitamins and supplements during radiation therapy may interfere with the body's performance. Therefore, this study aims to investigate the interference of vitamins and supplements with radiation therapy. Search Method: This review study used an internet search of indexed articles in Persian and English databases, including SID, PubMed, Scopus, Medline, Google Scholar, and Web of Science, from 2016 to 2022. The keywords used in the search included "vitamin", "supplement", "radiation therapy", "radiotherapy", "chemo", and "cancer treatment". Relevant articles were extracted and evaluated. In the initial search, 136 articles were found with relevant keywords. Finally, based on the research criteria and evaluation of titles, abstracts, and full-texts, 42 articles were reviewed. Results: The studies showed that the interference of vitamins and supplements with radiation therapy may lead to a decrease in therapeutic efficacy and an increase in side effects. High consumption of vitamins C and E may be associated with reduced effectiveness of radiation therapy. Likewise, high intake of antioxidant supplements such as beta-carotene, selenium, and vitamin A may reduce the effectiveness of treatment and increase the risk of side effects. Conclusion: To prevent interference between vitamins and supplements with radiation therapy, a complete evaluation of all vitamins and supplements that the patient is taking should be conducted before starting treatment, and if necessary, their consumption should be limited to avoid interference with radiation therapy. In general, maintaining a proper and varied diet can help reduce the risk of interference with radiation therapy.