Background: Little is known about the efficacy and safety of single balloon enteroscopy (SBE) in patients with Peutz-Jeghers syndrome (PJS). The aim of this study was to assess the efficacy and safety of SBE for treatment of small bowel polyps in patients with PJS. Methods: We conducted a single center observational study, which included all patients diagnosed with PJS who underwent SBE for polypectomy between January 2018 and March 2021. Complete treatment was defined as the absence of polyps≥20mm after SBE resection. The clinical records were retrospectively reviewed. Results: 102 patients (including 40 men and 62 women) with a mean age of 28.7 years (range 13-55y), were enrolled in our study. The intubation depth via oral approach of patients with history of laparotomy was significantly shorter than that of the patients without history of laparotomy ([241.6±64.2] cm vs [280.9±40.2] cm, P = 0.008). The maximum size of the resected polyps via anus during the second hospitalization was significantly smaller than that during the first hospitalization ([2.25±1.29] cm vs [4.26±3.51] cm, P = 0.032). Complications occurred in 10/129 of hospitalizations (4 delayed bleeding, 3 perforation, and 3 acute pancreatitis). Conclusions: SBE is effective and safe for resection of small bowel polyps in patients with PJS.