Deinococcus radiodurans shows extreme resistance to a range of remarkable environmental stresses. Deinococcal exopolysaccharide (DeinoPol) is a component of the cell wall, but its role in stress resistance has not yet been well-described. In this study, we isolated and characterized DeinoPol from Deinococcus radiodurans R1 strain and investigated its application as an antioxidant agent. Bioinformatic analysis indicated that dra0033, encoding an ExoP-like protein, was involved in DeinoPol biosynthesis, and dra0033 mutation significantly decreased survival rates in response to stresses. Purified DeinoPol consists of different monosaccharides and has a molecular weight of approximately 80 to 100 kDa. DeinoPol also demonstrates highly protective effects on human keratinocytes in response to stress-induced apoptosis by effectively scavenging ROS. Taken together, these findings indicate that DeinoPol is the first reported deinococcal exopolysaccharide that might be used in cosmetics and pharmaceuticals as a safe and attractive radical scavenger. Exposure to ultraviolet (UV) radiation can generate reactive oxygen species (ROS), resulting in DNA, lipid, and protein damage in cells and tissues such as the skin 1 , which becomes mildly inflamed, leading to photo-aging and carcinogenesis 2,3. The ROS and free radicals that are generated tend to stabilize themselves by scavenging electrons from biomolecules, triggering the activation of many cellular signaling cascades, including apoptosis and necrosis 4. A broad spectrum of natural antioxidants such as flavonoids, polyphenols, and sterols may be deployed to lessen these effects 5,6,7. Given their low negative effect on organisms and the environment, natural products with photo-protective properties are increasingly used to prevent radiation-induced skin damage. Recent research has shown that polysaccharides from natural products possess wide-ranging beneficial therapeutic effects and health-promoting properties 8. Bacterial exopolysaccharides (EPSs) are mostly nontoxic natural biopolymers with extensive applications in areas such as pharmaceuticals, nutraceuticals and functional foods, cosmetics, and insecticides 9-13. An extreme resistance to ionizing radiation, desiccation, UV radiation, oxidizing agents, and electrophilic mutagens has been observed in Deinococcus radiodurans 14. This is attributed to an enhancement of functional redundancies in both efficient protection from ROS by protein and lipid modifications and in DNA repair mechanisms 15. These characteristics are of interest in developing it for bioremediation of radioactive wastes and biomolecule production. The deinococcal cell envelope consists of a fragile, soft layer containing carotenoids, lipids, proteins, and EPSs 16,17. However, whether it has protective capacities against ROS-induced cellular damage remains poorly understood.