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Effect of submucosal injection of normal saline and glycerol fructose on endoscopic polypectomy in patients with colorectal polyps was investigated. A total of 275 patients with colorectal polyps were enrolled in this study and underwent endoscopic gastrointestinal polypectomy in Qingdao Chengyang People's Hospital from March 2013 to December 2016. Among them, 150 patients who underwent submucosal injection of glycerol fructose were set as the experimental group, and 125 patients who underwent submucosal injection of normal saline were set as the control group. The surgery conditions, complications and recurrence rates were compared between the two groups. The time of processing polyps and the total surgery time in the experimental group were shorter than those in the control group (P&lt;0.05). The number of repeated injections in the experimental group was less than that in the control group, and the difference was statistically significant (P&lt;0.05). The amount of fluid and propofol injected in patients of the experimental group was significantly lower than that of the control group, and the difference was statistically significant (P&lt;0.05). The en bloc resection rate (EBRR) and complete resection rate (CRR) in the experimental group were 68.0 and 48.0%, respectively. EBRR and CRR in the control group were 49.6 and 27.2%, respectively. EBRR and CRR in the experimental group were significantly higher than those in the control group (P&lt;0.05). After follow-up of the patients for 3 months, there was no significant difference in the recurrence rate between the two groups (P&gt;0.05). The results indicated that endoscopic colorectal polypectomy with glycerol fructose as a submucosal injection can shorten the time of surgery, reduce the number of repeated injections, reduce the amount of fluid and propofol, and also improve EBRR and CRR.