OBJECTIVE: To compare the gastrointestional (GI) adverse events of glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors by systematic review and meta-analysis to provide reference for clinicians. METHODS: The following databases were searched: Pubmed, Embase, Cochrane, ClinicalTrials, and CNKI. And the following terms were used to search head to head studies comparing the GI adverse events of GLP-1 receptor agonists and DPP-4 inhibitors: "GLP-1 receptor agonist", "DPP-4 inhibitor", "incretin-based therapy", "adverse events", and "safety". Meta-analysis was performed by Revman 5.0 software, with results expressed as odds ratio (OR) and 95% confidence interval (CI) for GI adverse events. RESULTS: A total of 1 231 articles were obtained, among which six randomized clinical trials (RCTs) which include 884 GLP-1 receptor agonists users and 798 DPP-4 inhibitors users (total number=1 682), were included for the meta-analysis. The result showed that GLP-1 receptor agonists were associated with a higher incidence of GI adverse events, the ORs of high dose GLP-1 receptor agonists versus DPP-4 inhibitors for nausea, vomiting, diarrhea, and constipation were 4.68(3.36, 6.52), 4.66(2.51, 8.65), 2.17(1.54, 3.06) and 2.39(1.35, 4.24), respectively; the ORs of low dose GLP-1 receptor agonists versus DPP-4 inhibitors for nausea, vomiting, diarrhea, and constipation were 4.09(3.06, 5.48), 3.80(2.22, 6.50), 2.06(1.46, 2.93) and 2.39(1.35, 4.24), respectively. CONCLUSION: Compared to DPP-4 inhibitors, GLP-1 receptor agonists are associated with a higher incidence of GI side effects including nausea, vomiting, diarrhea, and constipation.