Background: The association between the insulin receptor substrate-1 (IRS1) rs1801278 polymorphism and the risk of gestational diabetes mellitus (GDM) remains controversial based on existing published data. A meta-analysis was conducted to evaluate the potential correlation between the IRS1 rs1801278 polymorphism and GDM risk. Methods: Eligible studies were identified by conducting comprehensive searches in PubMed, Embase, Web of science, the China National Knowledge Infrastructure, and the Chinese Biomedicine databases. Pooled odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated using appropriate fixed-effects or random-effects models to evaluate the relationship between IRS1 rs1801278 polymorphism and the risk of GDM. Results: A total of nine studies were included in this meta-analysis, and the pooled analysis indicated no significant association between IRS1 rs1801278 and the risk of GDM. Heterogeneity among the studies was detected, and a Galbraith plot analysis was conducted to explore the source of heterogeneity. It was revealed that one study was responsible for the heterogeneity. After excluding this study, the heterogeneity decreased significantly. Conclusions: The present meta-analysis reveals that IRS1 rs1801278 polymorphism may not be correlated with GDM risk. The study was registered on PROSPERO (https://www.crd.york.ac.uk/prospero/), registrationnumber: CRD42023460095.