Most platelet-derived oxidants are produced through NAD (P) H-oxidase enzyme system. There are antioxidants such as superoxide dismutase and reduced glutathione in platelet. Oxidative stress alters platelet functions via regulation of platelet aggregation phase, impact on platelet nitric oxide and alpha II bbeta3 integrin, and imbalance between reduced and oxidized glutathione in platelet. Activated platelet by oxidative stress can influence blood vessel endothelium cell function, and worsen atherosclerosis through CD40 ligand. LDL is modified to oxidized LDL by platelets which can trigger foam cell formation. Some drugs with therapeutic intervention to reduce oxidative stress of platelet will be of use for atherosclerosis treatment.