Hyperlipidemia is a major risk factor for development of atherosclerosis. In the present study, the hypolipidemic effects of sumac (Rhus coriaria L.) fruits in high cholesterold diet (HCD)-fed rats was investigated. There was a significant (p < 0.001) increase in the levels of total cholesterol (TC) and triglycerides (TG) along with augmented activities of serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase. Treatment with aqueous methanol extract of sumac fruits reduced the above alterations observed in hypercholesterolemic rats. Sumac extract also reversed the hypertrophic cardiac histology. Furthermore, in vivo toxicological studies showed no evidence of acute toxicity of the extract in male Wistar rats. In conclusion, sumac fruit extract intervention minimized the lipid abnormalities and abnormal biochemical changes induced in HCD fed rats. This shows that sumac fruit extract possesses cardioprotective and hepatoprotective activities which will be beneficial in hypercholesterolemic condition.