Chalcone, flavone, and arylideneflavanone derivatives bearing one or two 3,5-di-tert-butyl-4-hydroxyphenyl groups were synthesized from 2′,4′-dihydroxyacetophenone and 3,5-di-tert-butyl-4-hydroxybenzaldehyde. These flavonoids were converted into the corresponding malonates and then reacted with C60 to yield the title compounds. The O–H bond dissociation enthalpies (BDE) and the chain-breaking antioxidant activity of the flavonoid derivatives and the corresponding C60 conjugates were evaluated. These results are consistent with the phenolic moiety being the main responsible for the reaction with peroxyl radicals, while the C60 part of the molecule acts synergically by trapping alkyl radicals under reduced O2 partial pressure. These novel C60–flavonoid conjugates are therefore promising leads for broad-spectrum radical scavengers.Graphical abstract