Objective To investigate the effects of dexmedetomidine combined with intraoperative thermal insulation on postoperative cognitive function, cellular immune status and inflammatory markers in patients undergoing radical resection for colorectal cancer. Methods Fifty patients who underwent radical resection of colorectal cancer in our hospital from March 2020 to September 2021 were selected and divided into observation group (26 cases with dexmedetomidine combined with intraoperative thermal insulation intervention) and control group (24 cases with conventional anesthesia management). The evaluation measures included the mini-mental state scale (MMSE) score, CD4+ T cell, CD8+ T cell ratio and CD4+/CD8+ ratio, the level of inflammatory markers (IL-6, TNF-α, CRP), and the incidence of postoperative complications. Results The MMSE score of the observation group was significantly higher than that of the control group on the 3rd day after operation (p < 0.001). After treatment, the proportion of CD4+ T cells, the proportion of CD8+ T cells and the ratio of CD4+/CD8+ in observation group were higher than those in control group (p < 0.01), while the inflammatory markers IL-6, TNF-α and CRP were lower than those in control group (p < 0.01). The incidence of postoperative cognitive dysfunction (POCD) in the observation group (7.69%) was significantly lower than that in the control group (33.33%) (p = 0.010), and the postoperative infection rate was also significantly decreased (p = 0.042). Conclusion Dexmedetomidine combined with intraoperative insulation can significantly improve postoperative cognitive function, maintain immune balance, reduce inflammatory response, and reduce the incidence of POCD and other postoperative complications in patients with radical resection of colorectal cancer.