As a unique medical system, traditional Chinese medicine (TCM) is an important part of the world’s traditional medicine. However, due to the complexity of TCM components and the compatibility of multiple TCM ingredients, the mechanism of its efficacy has not been completely defined, which hinders the modernization process of TCM to a certain extent. Urine is not subjected to homeostatic control, allowing it to reflect the sensitive changes that occur in the body. In this study, rat models were developed for intragastric administration utilizing two traditional Chinese medicinal formulations: Compound Danshen Dripping Pills and Huoxiangzhengqi Oral Liquid. Urine samples were collected before and after intragastric administration. Liquid chromatography-mass spectrometry (LC-MS/MS) was employed to identify the differential proteins in the urine of the rats before and after the treatment, and to analyze the biological pathways associated with these differential proteins. Compared with the control (before intragastric administration), a total of 84 differential proteins were identified in the model group of Compound Danshen Dripping Pills. A total of 64 different proteins were identified in the model group of Huoxiangzhengqi Oral Liquid. Furthermore, the biological pathways enriched by differential proteins of Compound Danshen Dripping Pills group are associated with their mechanisms of action in the treatment of cardiovascular diseases, such as glycolysis, lipid metabolism. The results indicate that urine proteomics can directly and systematically reflect the overall impact of traditional Chinese medicine on the body, which provides a new method to study the efficacy of traditional Chinese medicine.