OBJECTIVE: To evaluate the effect of Weichang'an pill (, WCAP) on functional dyspepsia (FD) and explore its regulation of brain-gut peptides (BGPs) and gut microbiota balance as a potential treatment mechanism. METHODS: The "0 ℃ saline gavage + irregular feeding and tail clamp" method was used to establish the FD rat model, excluding the normal group. The successfully established FD rat models were randomly divided into the model group and the WCAP1 (WC1), WCAP2 (WC2), WCAP3 (WC3), WCAP4 (WC4), WCAP5 (WC5), and Domperidone (Dom) groups ( 10 per group). The unhandled rats were designated as the control group. The gastrointestinal motility of the rats was evaluated using the charcoal propulsion test. Histopathology was assessed by hematoxylin and eosin (HE) staining. The enzyme-linked immunosorbnent assay method was used to detect the levels of motilin (MTL), gastrin (GAS), vasoactive intestinal peptide (VIP), and somatostatin (SS) in the serum from each group. In addition, the gut microbiota composition of fecal samples was analyzed using 16S rRNA sequencing. RESULTS: Rat models were successfully established according to data from rat state, gastrointestinal motility assessments, and HE staining. WCAP improved FD symptoms by accelerating the gastric emptying and small intestinal transit of FD rats. Mechanistically, WCAP increased the levels of GAS and MTL and reduced the levels of VIP and SS. Moreover, WCAP treatment restored the total relative abundance of Firmicutes and Bacteroidetes, increased the species richness of the gut flora, and modulated the changes in the composition and function of the gut microbiota. CONCLUSION: WCAP can effectively promote the recovery of gastrointestinal motility disorders in FD rats. The mechanism may be related to regulating the secretion of BGPs and the composition of the gut microbiota.