Cow’s milk contains bioactive secondary phenolic compounds that are formed by bovine’s gut bacterial flora from plant phenolic compounds. Equol, a metabolite of daidzein, is one such secondary compounds of biological interest. The potential of phenolic compounds in milk as dietary antioxidants and their distribution within the milk matrix were examined. The equol concentrations, total phenolic contents, and antioxidant activity (Trolox equivalent antioxidant capacity and inhibition of F2-isoprostanes formation by human neutrophils in vitro) were measured and compared in commercial cow’s milk of varying lipid contents. The Trolox equivalent antioxidant capacity and ability to inhibit F2-isoprostanes formation in vitro increased with the concentrations of phenolic compounds and equol in the milk. Equol and total phenolic compound concentrations correlated positively with the milk lipid concentrations. Separate experiments using homogenized and non-homogenized milk showed that dairy equol and phenolic compounds distributed to larger extent in the lipid fraction than in the aqueous fraction of cow’s milk. Our results showed that cow’s milk may serve as a dietary source of unique phenolic compounds, such as equol. Skimming of cow’s milk may reduce the original amount of equol and phenolic compounds and thereby diminishes the overall nutritive value and functional properties of cow’s milk.