Objective To explore the impact of clinical nursing pathway management on compliance, fatigue, and complications in colorectal cancer patients undergoing chemotherapy. Methods A study was conducted on 80 colorectal cancer patients undergoing chemotherapy admitted to Tianjin People’s Hospital from January 2023 to July 2024. Patients were randomly divided into a control group (n=40) and an observation group (n=40) using a random number table. Both groups received conventional nursing care, and the observation group was supplemented with clinical nursing pathway management. The chemotherapy compliance, complications, and cancer fatigue scale (CFS) scores of two groups of patients were compared. Results After intervention, the chemotherapy compliance of the observation group was higher than that of the control group, and the di?erence was statistically signi?cant (P < 0.05). The incidence rates of various complications in the observation group were lower than those of the control group, with all di?erences being statistically signi?cant (P < 0.05). Before the intervention, there was no di?erence in CFS scores between the two groups of patients (P > 0.05). After the intervention, the CFS scores of the observation group were lower than those of the control group, with a statistically signi?cant di?erence (P < 0.05). Conclusion The application of clinical nursing pathway management during chemotherapy for colorectal cancer patients can e?ectively improve cancer-related fatigue, increase patient compliance with chemotherapy, and reduce the occurrence of complications.