Objective To determine the effects of Dendrobium nobile Lindl. on the regulation of lipid metabolism based on metabolomics.Methods Twenty-four rats were randomly divided into the normal control and D. nobile treatment （0.25 g/kg） groups. Rats were intragastrically administered their assigned treatment once every 6 h for 5 d. After the last treatment， the plasma and liver of the animals were collected. Metabolomics were evaluated using UPLC-MS. Principal component analysis （PCA）， cluster analysis， and KEGG pathway analysis were performed to assess the metabolomics data. Compared with the normal control group， different metabolites were identified in the D. nobile treatment group. The expression levels of lipid metabolism-related genes were validated using quantitative real-time PCR.Results Obvious differences were found between the normal control group and D. nobile treatment group， with significant differences obtained for 1 448 metabolites （P<0.05） and a fold change greater than 2 recorded for 641 metabolites. Based on KEGG pathway analysis， metabolic pathways， biosynthesis of antibiotics， ABC transporters， biosynthesis of amino acids， protein digestion and absorption were among the top five pathways. D. nobile could significantly upregulate the gene expression levels of Cyp27a1 and Cyp3a1 （P<0.05） and significantly downregulate the gene expression of Lpin1 （P<0.05）.Conclusion Overall， D. nobile could regulate lipid metabolism. Such findings provide a scientific basis for the further development and utilization of D. nobile.