Effects of extracts obtained from the flowers of Elsholtzia splendens on the serum lipid profile and hepatotoxicity in mice were investigated. Female ICR mice were given E. splendens ethanolic extract (ESEs) orally at a dose of 10 or 50 mg/kg BW for 50 days. Significant dose-dependent decreases in triglyceride and low-density lipoprotein (LDL)-cholesterol of serum were observed. In addition, ESEs prolonged the lag-time of LDL oxidation in vitro. In the serum of ICE mice given ESEs orally at 10 and 50 mg/kg BW, the serum levels of aspartate aminotransferase (AST) and lactic dehydrogenase (LDH) increased significantly, while total protein, albumin, creatinine, alanine aminotransferase (ALT), and total bilirubin did not change. Therefore, ESEs may be beneficial to human health, although it has some hepatotoxicity.