The effects of proso millets on the antioxidant activity of liver were evaluated by the high-fat diet C57BL/6 mice model, and the relationship of antioxidants with the contents of main bioactive compounds in proso millets were also studied based on the chemical and cellular analyses of the polyphenols and flavonoids contents. The results showed that the high-fat diet reduced the hepatic antioxidant capacity of liver, while the addition of proso millets could improve it significantly with a high-fat diet. The contents of both polyphenols and flavonoids were significantly different among different breeds of proso millets. The variation coefficient of total polyphenol was 63.61％, ranging from 0.78 to 3.44 mg/g, while that of the total flavonoid content was 68.46％, ranging from 0.89 to 10.17 mg/g. The Oxygen Radical Absorbance Capacity (ORAC) and cellular antioxidant activity (CAA) of different breeds of proso millets were found different. Moreover, both of the ORAC and CAA of proso millet were correlated with the total contents of polyphenols and flavonoids, shown a positive linear relationship, and the linear coefficients (R²) were 0.81 and 0.57, respectively.