The effect of luteoloside on the regulation of lipid metabolism imbalance in obese mice and its mechanism were investigated. After 12 weeks of luteoloside (25, 50 and 100 mg/kg), obesity-related indicators were analyzed, such as serum, liver and adipose tissue indexes as well as gut microbiota and liver tissue-related protein expression levels. The results suggested that luteoloside intervention could reduce body fat mass and fat storage, improve lipid levels, glucose tolerance, and alleviate inflammatory disorders, especially in medium-dose treated mice. The serum levels of TC, TG, LDL-C in the HFD + M group decreased by 25.74 %, 42.03 %, 29.61 %, respectively, while HDL-C levels increased by 27.45 %. The levels of ALT and AST decreased by 44.15 % and 33.00 %, respectively. The intervention of luteoloside improved the variegation of gut microbes, more specifically, it balanced homeostasis of gut microbiota in obese mice. Luteoloside could regulate the expression of PPARα protein and down-regulate the expression proteins related to lipid synthesis, thereby inhibiting lipid accumulation and regulating lipid metabolism. The purpose of this study was to elucidate the molecular mechanism of luteoloside regulating lipid metabolism imbalance in obese mice and to provide a rationale for it.