Objective <p>To investigate Jianpi Qutan Decoction (JPQT)’s effects on hepatic lipid metabolism via the PPARα-CPT1α pathway.</p> Methods <p>Eight male C57BL/6J mice served as controls; 32 ApoE^-/- mice were randomized into atherosclerosis (AS), atorvastatin calcium (AC), and low/medium/high-dose JPQT groups. Prior to the intervention, therapeutic targets of JPQT were analyzed using network pharmacology to provide a theoretical basis for subsequent experiments. The AS model was induced by a 12-week high-fat diet. Hepatic triglyceride (TG) and cholesterol (TC) were measured via GPO-PAP. Glucose tolerance (GTT) and insulin tolerance (ITT) were assessed. Pro-inflammatory cytokines were analyzed by ELISA/colorimetry. Fatty acid metabolism enzymes were evaluated using kits. PPARα-CPT1α pathway mRNA and protein expression were quantified via qPCR and Western blot.</p> Results <p>JPQT and AC reduced aortic plaque lipid deposition. JPQT significantly lowered hepatic TG/TC, blood glucose, insulin, and inflammation. It modulated fatty acid metabolism by promoting ACC phosphorylation, suppressing FAS and FFA while elevating FAβO, with dose-dependent efficacy. Additionally, JPQT upregulated PPARα, CPT1α, and ACOX1 mRNA and protein expression in the liver.</p> Conclusion <p>JPQT may improves lipid metabolism and reduces AS progression by activating the PPARα-CPT1α pathway, with higher doses yielding stronger effects.</p>