Obesity has become a major social problem related to health and quality of life. Our previous work demonstrated that FRT10 alleviated obesity in high-fat diet (HFD)-fed mice by alleviating gut dysbiosis. However, the underlying functions of FRT10 in regulating liver and cecum contents metabolism remain unknown. Liver and cecum contents metabonomics combined with pathway analysis based on ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) were performed to evaluate the alterations of metabolic profiles between obese control mice and obese mice in FRT10-treated groups. The orthogonal partial least squares discriminant analysis (OPLS-DA) score plots showed that there were significant differences in cecum contents and liver markers between experimental groups. In total, 26 potential biomarkers were identified in the liver and 15 in cecum contents that could explain the effect of FRT10 addition in HFD-fed mice. In addition, gut-liver axis analysis indicated that there was a strong correlation between cecum contents metabolites and hepatic metabolites. The mechanism of FRT10 against obesity might be related to the alterations in glycerophospholipid metabolism, primary bile acid biosynthesis, amino metabolism, and purine and pyrimidine metabolism. Studies on these metabolites could help us better understand the role of FRT10 in obesity induced by HFD.