This study aimed to explore the mechanisms of Buyang Huanwu Decoction(BYHWD) and its different fractions in treating hyperlipidemia, screen lipid-regulating active components, and optimize the formula ratio. Metabolites in drug-containing sera were identified. A total of 96 ICR mice were randomly divided into a blank group(12 mice) and a modeling group(84 mice). The modeling group was fed a high-fat diet for 6 weeks to establish a hyperlipidemia model, and then randomly divided into a model group, an atorvastatin group(2.600 mg·kg~(-1)), a BYHWD group(18.571 g·kg~(-1)), an alcohol precipitation group(1.496 g·kg~(-1)), a 30% fraction group(0.163 g·kg~(-1)), a 50% fraction group(0.113 g·kg~(-1)), and a 90% fraction group(0.060 g·kg~(-1)). Samples were collected after administration for three weeks. Serum lipid indices, hepatic cholesterol(CHO), triglyceride(TG), and total bile acid(TBA) levels were detected. Pathological changes in the liver and adipose tissue, as well as the mRNA and protein expression of lipid-related genes(sterol regulatory element-binding protein 2 [SREBP2], insulin-induced gene 1 protein [INSIG-1], 3-hydroxy-3-methylglutaryl-CoA reductase [HMGCR], liver X receptor alpha [LXRα], ATP-binding cassette transporter A1 [ABCA1], and cytochrome P450 family 7 subfamily A member 1 [CYP7A1]) in the liver, were also determined. The results showed that the alcohol precipitation and 30% fraction showed significant effects on lowering CHO, and the alcohol precipitation and 50% fraction exhibited better regulatory effects on white adipose tissue. Except for the 90% fraction, all the other had reduced hepatic CHO and TG levels. All groups showed an impact on TBA. BYHWD and its different fractions could regulate the expression of lipid-related genes and proteins in the liver. In conclusion, the BYHWD, alcohol precipitation, 30% fraction, and 50% fraction effectively treat hyperlipidemia by reducing hepatic CHO, but their mechanisms of action are different: the 50% fraction mainly inhibits CHO synthesis; the alcohol precipitation and 30% fraction focus on promoting CHO efflux; the alcohol precipitation has significant advantages in CHO conversion to bile acids.