Six structurally related flavonoids including two flavones apigenin and luteolin, one isoflavone genistein, and three flavonols, galangin, kaempferol and quercetin, are affected differently as radical scavengers by presence of Ca(II). Except for apigenin showing no reaction with Ca(II), other flavonoids all coordinate with Ca(II) to form 1 : 2 Ca(II)-flavonoid complexes confirmed by UV-vis and mass spectra. Coordination with Ca(II) for luteolin with the 3′, 4′-catechol group and for flavonols with 3-hydroxyl and 4-carbonyl significantly enhance the DPPH• scavenging efficiencies shown by stopped-flow spectra. Addition of Ca(II) shows no effect on radical scavenging rate of Genistein, as an isomer of apigenin, although both containing the same 4-carbonyl and 5-hydroxyl as a potential chelating group as confirmed by mass spectra and cyclic voltammetry. The two structure elements, 3′, 4′-catechol and the combination of 3-hydroxyl and 4-carbonyl, are identified as important factors for Ca(II) enhancement of radical scavenging of flavonoids. Coordination of Ca(II) to kaempferol forming a 1 : 2 Ca(II)-kaempferol complex at 3,4 site shows the most significant enhancement in radical scavenging efficiency by a factor of 4.4 compared to other investigated flavonoids.