A short-term study was carried out on Wistar strain rats to determine the effects of Xylopia aethiopica extract on serum and postmitochondrial fractions (PMFs) of visceral organs in experimental hypercholesterolemia. Animals received normal diet and were administered cholesterol orally by intubations at a dose of 40 mg/kg/0.3 mL, plant extracts at 250 mg/kg, and cholestyramine (Questran®, Bristol-Myers Squibb, Hounslow, United Kingdom) at 0.26 g/kg five times a week for 8 consecutive weeks. Thereafter the hypolipidemic effects were assessed by measuring total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol, and triglycerides, whereas the extent of oxidative stress was assayed by measuring thiobarbituric acid-reactive substances and enzymatic antioxidants such as superoxide dismutase, catalase, and reduced glutathione (GSH) in serum and PMF of liver and kidney. We assayed two liver biomarkers-alanine aminotransferase and aspartate aminotransferase-for safety of X. aethiopica at the dose given in this experiment. Cholesterol feeding resulted in a significant increase (P < .05) in body weight of the hypercholesterolemic animals relative to control animals, and administration of X. aethiopica (250 mg/kg) caused a more than 60% reduction in body weight. Simultaneous treatment with X. aethiopica and Questran elicited 33.75% and 23.94% reductions, respectively, in serum cholesterol levels of hypercholesterolemic rats. In addition, the LDL-C level decreased significantly (P < .05) by 49.09% and 78.92% in serum and by 64.97% and 37.29% in the liver with cotreatment with the plant extract and Questran, respectively, compared to untreated hypercholesterolemic rats. X. aethiopica counteracted the decreases in enzymatic antioxidants, especially in GSH, where there was a greater than 300% increase compared with hypercholesterolemic animals. This study has shown that intake of X. aethiopica reduced the composition of lipids and produced a favorable lipid profile in the serum and PMF of visceral organs in experimental hypercholesterolemia.