Obesity is a severe public health problem worldwide. Our study aims to assess whether a saponin-enriched extract from the leaves of Boussingaultia gracilis (SBG) could attenuate obesity and its related metabolic disorders in mice and to explore the potential mechanism of this effect. Three-week old male mice were fed with a HFD for 7 weeks followed by a 10-week period in which the mice were supplemented with distilled water or SBG (250 mg per kg bodyweight). We demonstrated that SBG supplementation for 10 weeks mitigated obesity and its complications in diet-induced obesity (DIO) mice, such as reducing the hepatic damage underlying steatosis, modulating lipid metabolism, enhancing adipocyte thermogenesis, restoring insulin sensitivity and glucose homeostasis, and alleviating inflammation status. Finally, we established an untargeted metabolomics approach based on UPLC-MS to profile the metabolic changes in liver tissue and thereby discovered novel potential biomarkers to clarify the mechanisms of action of SBG in treating a mouse model of DIO. Thirty-nine potential biomarkers and five metabolic pathways contributing to the beneficial effect of SBG were discovered and identified.