Abstract: By revealing the interaction mechanism between flavonols and Cu(Ⅱ), the antioxidant activity of flavonol-Cu(Ⅱ) coordination compounds was enhanced. The effects of hydroxyl deprotonation and bound Cu(Ⅱ) on the molecular structure and antioxidant activity of three forest-derived dietary flavonols, namely, kaempferol, quercetin, and myricetin, in aqueous solution were analyzed by density-functional theory B3LYP method. The results showed that after deprotonation of hydroxyl group, the length of other O—H bonds in the molecule decreased, the dihedral angle of the benzene ring structure changed, the dipole moment of the molecule increased, the energy level difference(ΔE) between the highest occupied molecular orbital(HOMO) and the lowest unoccupied molecular orbital(LUMO) decreased, and the positive charge number of other hydroxyl atoms in the molecule decreased. The other O—H bond lengths in the molecule increased, the dihedral angle and dipole moment changed, ΔE decreased, and the positive charge number of hydroxyl atoms increased after combining with Cu(Ⅱ). It was also found that the deprotonated flavonols mainly enhanced the ionic activity by changing the molecular structure and decreasing the ΔE, and formed a higher negative potential at the deprotonation site, thereby coordinating with Cu(Ⅱ) through electrostatic interactions. The flavonols bound to Cu(Ⅱ) mainly promoted the binding with free radicals by increasing the bond lengths, changing the molecular structure, and increasing the number of positive charges of the hydrogen atoms, while decreasing the ΔE to enhance the molecular activity and strengthen its antioxidant ability.