In the present study, we have addressed novel MsrA‐catalytic antioxidant defense. We found that low‐molecular sulfides, such as DMS, could serve as the substrate of MsrA to scavenge oxidative stressors. The lone pair electrons on the methylthiol‐sulfur nucleophilicity of sulfide attack the sulfenic sulfur in active site to form the positively charged sulfonium intermediate. Then, MsrA catalyzes the transition and releases the sulfoxide. It should be noted that DMS and other thiomethyl‐containing compounds, such as free methionine, methyl mercaptan, and dimethyl disulfide, may work synergistically with the Met residues. An MsrA‐regulated endogenous catalytic antioxidant network of low‐molecular methyl sulfides may also confer a good antioxidation defense in vivo.