Hyperlipidemia is a major risk factor for development and progression of CVD. This study evaluates the potential effect of grapeseed, ginger and mustard oils (5% and 10%) on serum lipid, liver, renal function tests (SGPT, SGOT, creatinine, uric acid and urea) and antioxidant enzymes (catalase and superoxide dismutase) of high fat diet rats. Forty-eight male rats divided into 8 groups; G1 fed standard diet (negative control), seven groups fed hyperlipidemic, for 6 weeks, one kept as positive control fed hypercholesterolemic diet, six groups fed hypercholesteremic diet with tested oils. Total cholesterol, triglycerides, high, low, very low-density lipoproteins, liver, renal function tests and antioxidant enzyme activity measured. Hypercholesterolemic rats showed a significant elevation in TC (99.66 ± 0.88), TG (60.33 ±4.33), LDL-c (57.00 ± 0.57), VLDL-c (12.00 ± 0.57) and reduction in serum HDL-c (20.66 ± 0.88) compared with negative control (76.00 ±0.57, 42.00 ±3.51, 40.33 ± 1.45, 8.40 ± 0.66 and 30.66 ± 0.88 respectively). Also, liver and renal function tests showed significant elevation and antioxidant enzyme showed significant reduction. Tested oils with different concentrations were effective in reducing lipids, restoring antioxidant enzymes activity and HDL-c. Histopathological examination of liver, renal, heart and aorta of hypercholesterolemic rats showed vacuolation of some cells, intramuscular hemorrhage and edema, inflammatory cell infiltration. Tested oils preserved normal structure of liver, kidney, heart and aorta. This study confirmed the health benefits of tested oils in modulation of lipid profile, kidney, liver function tests and antioxidant enzymes activity. Also modulate histopathological changes of examined tissues.