Abstract: Free radicals and reactive oxygen species(ROS) generated by ionizing radiation attack vital macromolecules, such as DNA, lipids and Proteins, thus causing cell and tissue damage. The major source of radiation-induced ROS production is believed to be associated with mitochondria. Removal of excessive mitochondrial reactive oxygen species by electron scavengers and antioxidants is a promising therapeutic strategy to reduce the detrimental effects of radiation exposure. Mitochondrial targeting antioxidants and electron scavengers have been suggested as promising radioprotectors due to their well ability to remove of excessive mitochondrial reactive oxygen species. Papers about mitochondrial targeting drug delivery systems have been publicated in recent years. Technique of mitochondrial targeting drug delivery system, potential application in radiation protection and its development trend are discussed in this review.