<p>Dioxinodehydroeckol (DOO) is a natural phlorotannin with remarkable potential antioxidant activity. In this study, for the first time, the mechanism and kinetics of its radical scavenging activity specifically targeting hydroperoxyl radicals under physiological conditions (both aqueous and lipid environments) were elucidated. This compound was initially evaluated through its intrinsic thermochemical properties based on mechanisms such as formal hydrogen atom transfer (fHAT), sequential electron proton transfer (SETPT), and sequential proton loss electron transfer (SPLET). The kinetic calculations revealed that the reaction rates (<i>k</i>_overall) of DOO with HOO• radicals in aqueous and less polar phases (pentyl ethanoate) were 3.76 × 10²&#xa0;M⁻¹&#xa0;s⁻¹ (when considering the influence of the molar fraction of HOO• for the water environment) and 1.54 × 10⁵&#xa0;M⁻¹&#xa0;s⁻¹, respectively, with the rate in the pentyl ethanoate phase particularly surpassing that of the reference antioxidant, Trolox. Furthermore, it was demonstrated that in aqueous conditions, the fHAT mechanism dominated over SPLET, as indicated by <i>k</i>_fHAT-total &gt; <i>k</i>_SET-total. These findings highlight DOO as a promising antioxidant with potency to scavenge HOO• radicals in lipid environments.</p>