5-[(E)-2-(4-Hydroxyphenyl)ethen-1-yl]benzene-1,3-diol (trans-resveratrol, RsvH3) is a stilbenoid, a kind of natural phenolic compound, 1 and a phytoalexin, which is found in mulberries, grapes, and red wine. RsvH3 shows a surprising number of health benefits, the mitigation of age-related diseases including carcinogenesis and neurodegeneration, and pharmacological activities such as anti-inflammatory and cardioprotective properties. Since their pathogenic seems to be related to reactive oxygen species (ROS) generated in several biochemical processes and pathologies, RsvH3 could be valuable as a multitarget molecule against several diseases. Therefore, ROS scavenging by RsvH3 has been studied for its potential therapeutic role, despite little obvious evidence of a substantial effect on any human disease or no high-quality evidence of health benefits in humans. Then, so far, it remains an important research subject in the fields of medicine, pharmacy, and human health. To prove the medicinal effect of RsvH3, which is based on its antioxidant activities, it is necessary to demonstrate the chemical reaction mechanism including electron transfer (ET) that scavenges ROS such as superoxide radical anion (O2 •-, a precursor of hydroperoxyl radical: HO2 • ), and hydroxyl radical (HO • ), apart from the biological antioxidant assay. That is, clarifying the mechanism of ROS scavenging by RsvH3 is a prerequisite to elucidate the related medicinal effect, since ROS generated around lesions and inflammatory organs may directly cause several pathologies. RsvH3 belongs to polyphenols' stilbenoids, possessing two phenolic rings linked to each other by an ethylene bridge (stilbene-double-bond). Numerous antioxidant studies of RsvH3 and related compounds have been reported using different assays and methodologies, with reference to the structure-activity or property relationship related to the number and position of the hydroxy group (OH). In these studies, the electron-donating ability of phenolic compounds such as RsvH3 for their antioxidant activity is discussed. Furthermore, experimental data demonstrate that if the OH is scavenged or replaced by the methoxy group, the molecule loses its activity, suggesting that OH plays a role as a proton donor besides as a substituent with an electronic inductive effect along the electron donation. Based on above, the ROS-scavenging activity has ever been evaluated using not only the ionization potential but also the bond dissociation energy of the OH as a key parameter, which presents the antioxidants-property of RsvH3 molecule and individual OH. Currently, it is considered that both proton transfer (PT) and ET are involved in the antioxidant mechanism. That is, hydrogen-atom transfer (HAT) from the OH group via hydrogen bond (HB) rather than single-electron transfer (SET) is closely related to the ROS-scavenging/antioxidant activity.