Objective. Heyi disease, Xila disease, and Badagan disease are three common diseases in Mongolian medicine. The changes in intestinal microbiota may be associated with the occurrence, development, and treatment of these diseases. This study aimed to investigate the effects of herbal treatment on intestinal microbiota and serum metabolites in rats with these three diseases. Methods. Firstly, Heyi, Xila, and Badagan disease model rats were established by environmental, diet, and drug intervention. Then, 16S rRNA gene sequencing and metabolomics analysis were used to analyze the changes in intestinal microbiota and serum metabolites after treatment. PICRUSt analysis was applied to predict the potential functions of intestinal microbiota, and OPLS-DA multivariate model was applied to screen differential serum metabolites. Results. 16S rRNA gene sequencing showed that herbal treatment significantly increased the species diversity and changed the composition of intestinal microbiota in Heyi disease and Xila disease rats. After treatment, there were 10, 9, and 3 bacterial biomarkers that were increased in Heyi, Xila, and Badagan disease rats, respectively. In the Heyi disease model, treatment resulted in 45 differential serum metabolites, involving 4 pathways. In the Badagan disease model, treatment resulted in 62 differential serum metabolites, involving 4 pathways. However, there was no significant difference in serum metabolites between TreatB and ConB in the Xila disease model. Conclusions. Herbal treatment significantly changed the intestinal microbiota and serum metabolites of rats with three Mongolian medicine diseases.