Nucleosides are sensitive sites towards oxidations caused by endogenous and exogenous oxidative resources, and a large number of the produced DNA lesions behave as pathogenesis eventually. We herein analyze oxidative modes of nucleosides and structure- activity relationships of some clinical nucleoside drugs. Together with our previous findings on the inhibitory effects of nucleoside derivatives against DNA oxidation, all these results imply a possibility for nucleoside to be a new member in the family of antioxidants. Then, some novel synthetic routines of nucleoside analogs are collected to reveal the applicability in the construction of nucleoside antioxidants. Therefore, it is reasonable to envision that the nucleoside antioxidant will be a novel topic in the research of both nucleosides and antioxidants.