As a Chinese herbal medicine used in East Asia for thousands years, Cortex Magnoliae Officinalis (CMO) was observed to possess a protective effect against OH-induced DNA damage in the study. To explore the mechanism, the antioxidant effects and chemical contents of five CMO extracts were determined by various methods. On the basis of mechanistic analysis, and correlation analysis between antioxidant effects & chemical contents, it can be concluded that CMO exhibits a protective effect against OH-induced DNA damage, and the effect can be attributed to the existence of phenolic compounds, especially magnolol and honokiol. They exert the protective effect via antioxidant mechanism which may be mediated via hydrogen atom transfer (HAT) and/or sequential electron proton transfer (SEPT). In the process, the phenolic-OH moiety in phenylpropanoids is oxidized to the stable quinine-like form and the stability of quinine-like can be ultimately responsible for the antioxidant.