The aim of this investigation was to compare the influence of naringin versus red grapefruit juice on plasma lipid levels and plasma antioxidant activity in rats fed cholesterol-containing and cholesterol-free diets. The antioxidant activity of a correlated quantity of red grapefruit juice was higher than that of naringin. Forty-two male Wistar rats were randomly divided into six groups of 7 named control, naringin, grapefruit, Chol, Chol/naringin, and Chol/grapefruit. The rats of the control group were fed basal diet (BD) and 1-2 mL of distilled water. To the BD of the other five groups were added 0.46-0.92 mg of naringin dissolved in 1-2 mL of distilled water (naringin), 1-2 mL of red grapefruit juice (grapefruit), 1% of nonoxidized cholesterol (NOC) and 1-2 mL of distilled water (Chol), 1% of NOC and 0.46-0.92 mg of naringin in 1-2 mL of water (Chol/naringin), and 1% of NOC and 1-2 mL of red grapefruit juice (Chol/grapefruit). After 30 days of different feeding, it was found that diets supplemented with red grapefruit juice and to a lesser degree with naringin improved the plasma lipid levels mainly in rats fed cholesterol and increased the plasma antioxidant activity. In conclusion, naringin is a powerful plasma lipid lowering and plasma antioxidant activity increasing flavonone. However, fresh red grapefruit is preferable than naringin: it more effectively influences plasma lipid levels and plasma antioxidant activity and, therefore, could be used as a valuable supplement for disease-preventing diets.