Previous studies had indicated that the gut microbiota was a main internal factor leading to obesity through energy storage and metabolic disorders. Lycium Barbarum Polysaccharides (LBP) have been discovered with a more protective effect on intestinal flora. But it is unclear whether LBP could regulate the gut microbiota to modulate metabolites, finally relieving obesity. A related study of high-throughput 16S rRNA sequencing and serum metabolomics profiling in LBP intervention on high fat diet-induced obese rats then explored the beneficial effects of LBP and the underlying mechanism. LBP affected lipid parameters such as total cholesterol, Triglyceride, and High-density lipoprotein. The gut microbiota result detected 16 types of the phylum of bacteria in total, while four of them (Bacteroidetes, Firmicutes, Proteobacteria, Deferribacteres) were significantly different. LBP upregulated the level of Firmicutes of obese rats. LBP might associate with the gut microbiota that participates in the membrane transport and metabolism of amino acid, carbohydrate, energy, and lipid. The serum metabolomics profiling of high-fat diet-induced obesity rats found over 30 differential metabolites between model and intervention groups. Primary metabolites include cortisol, glycohyocholic acid, homo-L-arginine, ursodeoxycholic acid, isoursodeoxycholic acid, glycoursocholic acid, 4-ethylphenylsulfate, deoxycholic acid, 7-hydroxy-3-oxocholanoic acid isomers, gly-phe, pipecolic acid, proline betaine, and pyrocatechol sulfate. Pathway analysis in serum found four disorder pathways: glycerophospholipid metabolism, glycine-serine-threonine metabolism, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism. The studies revealed that LBP treatment increased the diversity of fecal microorganisms and reduced metabolic disorders in obese rats. LBP ameliorated metabolic disorders and rebalanced the gut microbiome.