Radiation-induced changes in normal cells, including their mitochondria, from around the tumor can lead to the development of remote complications that negatively affect the effectiveness of radiation therapy. This determines the search for radioprotectors capable of overcoming the membrane barrier of mitochondria and suppressing their acquired dysfunction for selective protection of healthy tissues. The use of amifostine and melatonin radiomitigators, whose action is characterized by low toxicity, the ability to overcome acquired mitochondrial dysfunction, and unimpeded penetration into the mitochondria of various types of cells, is recognized as a reliable and effective means of protection. The appointment of the specified drugs to accompany radiation therapy of oncological patients is substantiated and recommended.