The empirical use of combination herbal medicines is common among both traditional communities and the standardized herbal medicine industry. Scientific data on the advantages and disadvantages of using combination herbal medicines are still lacking; hence conducting experimental study using animal models is necessary. Single purple sweet potato extract has been shown to reduce blood cholesterol levels, act as an antioxidant and increase SOD-2 and SOD-3 in the blood vessel endothelium. Red fruit extract also has a strong antioxidant effect. This study aimed to identify the most effective and safe combination of these extracts for the liver and kidneys. The subjects were 21 adult male Wistar rats, divided into three groups consisting of a control group and two intervention groups with a randomized pre and post-test control group design. The first intervention group received 100 mg/day purple sweet potato tuber extract and 0.2 ml/day red fruit extract with high cholesterol feed for four weeks, while the second group received 200 mg/day purple sweet potato tuber extract and 0.4 ml/day red fruit extract with high cholesterol feed for the same duration. The lipid profile, MDA, and SOD were measured before and four weeks after the treatment began. In addition, post-test data included measurements of SGPT, BUN, and serum creatinine. The study found that the combination of 200 mg purple sweet potato extract and 0.4 ml red fruit extract led to a significant improvement in lipid profile, with lower levels of MDA and higher SOD (p<0.05). The results of SGPT and BUN tests and serum creatinine also showed lower values than the control group. Thus, it is concluded that this combination is a safe and effective antioxidant and hypolipidemic for the liver and kidneys.