Lipid accumulation and metabolic disorders caused by a high-fat diet (HFD) pose significant threats to human health, and place a substantial burden on individuals and society. In this study, a novel combination comprising three traditional Chinese herbs (lotus leaf, hawthorn, and leaf of Chinese holly) and a probiotic (Bifidobacterium lactis BPL-1) (TCMP) was prepared. Then, its effects on growth performance, fat accumulation, hepatic function and gut microbiota in mice fed a high-fat diet were investigated. According to the results, TCMP significantly reduced adipose tissue fat accumulation, improved hepatic lipid metabolism, and ameliorated glucose homeostasis in HFD-fed mice. Notably, TCMP not only improved the abundance and diversity of gut microbiota and increased the content of beneficial intestinal bacteria related to lipid metabolism (especially Bifidobacterium animalis), but also increased the production of short-chain fatty acids, including2-methylbutyrate, isovaleric acid and isobutyric acid. Additionally, multi-omics (transcriptome and metabolome) analysis revealed that TCMP significantly inhibited the expression of genes involved in the lipid biosynthesis process and modulated the purine and glycerophospholipid metabolism caused by a high-fat diet, thereby achieving the purpose of reducing fat accumulation and regulating lipid metabolism. Taken together, our finding demonstrates the potential of TCMP as a promising therapeutic candidate for combatting obesity and lipid metabolism disorders induced by a high-fat diet.