The HOO• and O2•- scavenging activities of 12 natural anthocyanidins were investigated in physiological environments by using DFT calculations. The results suggest high HOO• scavenging activity in aqueous medium with overall rate constants in the range of koverall = 1.58 × 108 - 7.59 × 109 M-1 s-1, whereas in lipid medium only weak activity is predicted. O2•- scavenging is also fast in water with kapp = ∼109 M-1 s-1. Like in the case of many other antioxidants that contain acidic moieties, the anion states (H3A- and H2A2-) and the single electron transfer mechanism play a dominant role in the HOO• scavenging activity of anthocyanidins in water at pH = 7.4. Analysis of the mechanism suggests that the O2•- and HOO• radical scavenging can occur as a regeneration cycle that might increase the protective efficiency of anthocyanidins against oxidative stress.