Low glycemic index (GI) diets are recommended to reduce the risk for chronic diseases by managing postprandial elevations in blood glucose and insulin. However, to our knowledge, a systematic review of randomized controlled trials (RCTs) to investigate this relationship and interpret its clinical relevance has yet to be performed. This review aims to assess the effect of low versus high GI breakfast meals on postprandial glycemic and insulinemic responses in adults. Two researchers independently screened 1100 articles from PubMed, CINAHL, Medline, and Cochrane databases and extracted data from 11 qualified RCTs. Meta-analyses were performed to calculate overall effect sizes of postintervention blood glucose concentration change values at different time points (60, 90, and 120 min) using a random-effects model, reporting their weighted mean differences (WMDs) and 95% confidence intervals (CIs). Low GI breakfasts significantly reduced postprandial blood glucose concentrations at all time points: 60 min (WMD: -1.32 mmol/L; 95% CIs, -1.64 to -0.99), 90 min (WMD: -0.74 mmol/L; 95% CI, -0.92 to -0.56), and 120 min (WMD: -0.44 mmol/L; 95% CI, -0.63 to -0.26). Further analyses not only indicated similar trends following the stratification of studies according to the glycemic load, but also showed a more pronounced decline in glycemic response among individuals with metabolic impairments. These results highlight the benefits of lowering breakfast meal GI to provide clinically relevant reductions in acute glucose response.