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Objective: To explore the application of comfortable nursing in the preparation of colonoscopy in oral magnesium sulfate, and to provide scientific reference direction for nursing staff. Methods: 68 patients with colonoscopy were randomly divided into experimental group and control group (n = 34). In the control group, the routine nursing intervention was used, and the intervention group was treated with comfortable nursing intervention. Data analysis was performed using SPSS 20.0. Results: The total satisfaction score of the experimental group was (96.88 ± 1.26), the total satisfaction score of the control group was (80.65 ± 3.32), the test group (P < 0.05). The incidence of adverse reactions in the experimental group was significantly lower than that in the control group. The incidence of adverse reactions was 5.88% in the experimental group and 23.53% in the control group. Conclusion: The effect of comfortable nursing on the preparation of colonic gut in the oral magnesium sulfate method is relatively large.