Objective To explore the mechanisms involved in Xiangsha Liujunzi Tang intervention for functional dyspepsia (FD) in rats with spleen and stomach weakness via the CaM/ MLCK/ MLC20 pathway. Methods 60 SPF male SD suckling rats were randomly divided into blank (n= 10) and modeling (n= 50) groups. A comprehensive modeling method (gavage administration of iodoacetamide + exhaustion of swimming + disturbance of hunger and satiety) was used to replicate an FD rat model with spleen and stomach weakness. After successful replication of the model, the rats in the modeling group were randomly divided into a model; positive control; and Xiangsha Liujunzi Tang high-, middle-, and lowdose groups, with 10 rats in each group. Rats in the blank and model groups were given 10 mL/ (kg·d) normal saline; the positive control group was given 1. 35 mg/ (kg·d) mosapride; and the high-, middle-, and low-dose Xiangsha Liujunzi Tang groups were given 12, 6, and 3 g/ (kg·d) Xiangsha Liujunzi Tang, respectively. The intervention lasted 14 days. The general condition of each rat was observed before and after modeling and administration, and food intake and body mass were measured. After the intervention, the gastric emptying rate and intestinal propulsion rate were measured, and pathological changes to gastric tissue were observed by hematoxylin-eosin staining. The content of Mg²⁺ -ATP enzyme in the gastric tissue was determined biochemically, and the protein expression levels of CaM, MLCK, and p-MLC20 in gastric tissue were detected by Western Blot. Results Compared with the blank group, the model group rats had withered hair; lazy movements; slow actions; significantly reduced general survival score; and lower food intake, body mass, gastric emptying rate, and intestinal propulsion rate ( P< 0. 05), but there was no obvious abnormality in their gastric histopathology. The content of Mg²⁺ -ATP enzyme in the gastric tissue decreased, and the protein expression levels of CaM, MLCK, and p-MLC20 in the gastric tissue decreased significantly. Compared with the model group, the high- and middledose group rats had significantly improved general survival status scores, while their food intake, body mass, gastric emptying rate, and intestinal propulsion rate were significantly increased ( P< 0. 05), but there was no significant difference in gastric pathology. The content of Mg²⁺ -ATP enzyme and the protein expression levels of CaM, MLCK, and p-MLC20 in gastric tissue also increased significantly. The intervention effect of Xiangsha Liujunzi Tang was dose dependent. Conclusions Xiangsha Liujunzi Tang effectively improved the general condition and gastric motility of FD rats with spleen and stomach weakness. The specific mechanism may be related to the activation of the CaM/ MLCK/ MLC20 pathway in gastric tissue to regulate smooth muscle contraction and promote gastric motility.