Mulberry leaf has potential in lipid-lowering. Here, we compared the chemical composition and lipid-lowering effects of different mulberry leaf-derived teas, and investigated their underlying gut microbiome-related mechanisms. The main components of mulberry leaf-derived tea were flavonoids, phenolic acids and alkaloids, with green tea (0.60% polyphenols, 3.35% polysaccharides, 0.20% DNJ) containing higher levels than black tea (0.40% polyphenols, 2.95% polysaccharides, 0.15% DNJ). Accordingly, the lipid-lowering efficacy of green tea was superior to that of black tea in high-fat (HFD)-induced hyperlipidemic mice. Black tea increased 2 genera and 130 metabolites, decreased 6 genera and 90 metabolites, while green tea increased 5 genera and 127 metabolites, decreased 15 genera and 64 metabolites. Correlation analysis showed that the alterations of gut microbiota and metabolic profiles caused by mulberry leaf tea were tightly associated with its lipid-lowering effect. Altogether, this study provided a promising functional food targeting gut microbiota for the management of lipid metabolism.