Novel di-Mannich bases of cyclovalone derivatives (1) have been synthesized and evaluated their antioxidant activity using DPPH free radical-scavenger method. The structures of the compounds were confirmed on the basis of FT-IR, 1 H-NMR, 13 C-NMR and mass spectral data. The result of antioxidant evaluation showed that di-Mannich derivative of cyclovalone with diethylamine ((2E,6E)-2,6-bis({3-[(diethylamino)methyl]-4-hydroxy-5-methoxyphenyl} methylidene) cyclohexan-1-one) (2a) exhibited the highest antioxidant activity with IC 50 = 39.0 µM. Structure-activity relationship study showed that the higher pKa of the Mannich base, the higher activity (the lower IC 50 ) of the compound.