Objective This study (CRD42023464989) aimed to explore the effects of pre-operation immunonutrition on safety and immune related factors in colorectal cancer patients undergoing surgery. Methods We systematically searched PubMed, Embase, and Wanfang databases to collect all clinical randomized controlled trials of the application of pre-operation immunonutrition for patients with colorectal cancer, published until July 2023. The primary outcomes were safety and immune related factors. Results A total of 16 studies were finally included. Preoperative immunonutrition could reduce the postoperative infection rate (risk ratio (RR) = 0.56, 95% confidence interval (CI): 0.36, 0.88; p = .01), and wound infection rate (RR = 0.44, 95% CI: 0.27, 0.70; p < .001) in patients with colorectal cancer. For length of stay (mean difference (MD) = −1.10, 95% CI: −2.70, 0.49; p = .17), it was similar between groups. Meanwhile, patients in the pre-operation immune nutrition group also had significantly increased infiltrative lymphocytes CD16 + (MD = 0.04, 95% CI: 0.02, 0.06; p < .001), and CD56 + (MD = 0.05, 95% CI: 0.03, 0.06; p < .001) cells in the tumor tissues, compared to the control group. Conclusion Immunonutrition intervention has the potential to reduce postoperative infectious complications and improve tumor infiltrative lymphocytes in patients with colorectal cancer undergoing surgery.