Objective To evaluate the efficacy and safety of endoscopic trans-gastric gallbladder-preserving polypectomy in treatment of gallbladder polyps. Methods A retrospective analysis was performed on data of 25 patients with gallbladder polyps who underwent endoscopic trans-gastric gallbladder-preserving polypectomy in the endoscopy center of Zhongshan Hospital from September 2017 to August 2019. Completion of operation, operation time, postoperative hospital stay, complications and follow-up results of patients were obtained and analyzed. Results There were 13 cases of single polyp and 12 cases of multiple polyps, 13 cases of simple gallbladder polyps, and 12 cases of polyps and gallstones. The maximum diameter of polyps was 0.2-1.5 cm. The procedure failed in 1 patient (4%) because of the severe adhesion of abdominal cavity and disappearance of gallbladder when passing through the gastric wall. Twenty-four patients (96%) were successfully treated with endoscopic trans-gastric gallbladder-preserving polypectomy. The operation time was 67.1±26.8 min (35-140 min). The median hospital stay was 4 d (2-5 d). No severe adverse events including delayed bleeding, delayed perforation, diffuse peritonitis or abdominal abscess occurred. During the median follow-up time of 8 months (0-23 months), no patient was lost, no recurrence of polyps and no severe adverse events related to metal clips occurred. Conclusion Endoscopic trans-gastric gallbladder-preserving polypectomy shows good short-term efficacy and is technically feasible, however, long-term outcome still requires further research.