DMS scavenges ROS via its thiomethyl groups. The antioxidation of DMS may not only be due to its natural antioxidant activity. Recent discovery of a MsrA‐centered catalytic mechanism raises the possibility of the physiologically regulated oxidation of thiomethyl groups in organism (Wu et al., 2013a; Fan et al., 2015). Thus, the antioxidation effect of DMS after MsrA knockdown was observed. We found that MsrA activity was required for the beneficial effects of DMS against oxidative stress. Furthermore, we established a computational model to visualize structural interactions between DMS and MsrA. Under oxidative stress, ROS induced a sulfenic acid residue on Cys72 of MsrA, followed by the reaction between oxygen atom on CYO72 and S atom of DMS. The Phe73 and Trp74 in MsrA facilitated DMS to bind the active center via hydrophobic bond, and Tyr103 and Glu115 increased the oxygen atom transfer from the CYO72 to the S atom of DMS via hydrogen bond. The peroxidase activity of MsrA significantly facilitated the reactivity of DMS at a low concentration. Furthermore, MsrA may increase the antioxidation of DMS via other mechanisms. Under oxidative condition, the oxydation product of DMS, DMSO, has been historically recognized as a strong scavenger of free radicals, which may secondarily react with radicals. The reaction between DMSO and OH˙ may underlie the total radical‐scavenging capacity of DMS. Under reduced condition, MsrA can reduce DMSO back into DMS, which may be critical in the availability of DMS. The mechanisms of DMS‐mediated radical‐scavenging capacity were illustrated in Fig. 2A,B.