Surgery is the primary curative treatment for patients with nonmetastasized colorectal cancer (CRC). Rate of complications, morbidity, mortality, and overall survival of patients with CRC are factors associated with speed of recovery following surgery. Wuda granule (WD) is a traditional Chinese medicine (TCM) prescription used to promote rapid recovery after surgery. However, the specific mechanism of action of WD has not been characterized. Our study included 60 patients with clear histopathological evidence of colon or rectal cancer who underwent CRC laparoscopic surgery and 30 healthy individuals. Serum biochemistry and clinical evaluation of gastrointestinal function showed that WD could improve the nutritional status and gastrointestinal function and reduce the level of inflammation of patients with CRC following laparoscopic surgery. In addition, we used UPLC/Q-TOF-MS/MS-based metabolomics analysis to determine the mechanism of WD-related rapid recovery following laparoscopic surgery in patients with CRC. Twenty metabolites associated with arachidonic acid, alanine, aspartate and glutamate, alpha-linolenic acid, pyruvate, histidine, and glycerophospholipids were identified. The results suggested that the therapeutic mechanism of laparoscopic surgery combined with WD may be related to regulation of nutritional status, inflammation, immune function, energy, and gastrointestinal function in patients with CRC. This study also highlighted the ability of TCM compounds to interact with multiple targets to induce synergistic effects. This study may result in further studies of WD as a therapeutic agent to promote recovery following surgical resection of CRC tumors.