BACKGROUND The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide. GDM is associated with increased risks for mother and child during pregnancy and in later life. The aim of this article is to systematically review literature on the effectiveness of interventions to prevent GDM. METHODS Controlled trials found in PubMed, EMBASE, or CENTRAL were selected. The primary outcome was GDM, and relevant secondary outcomes were maternal fasting blood glucose and large-for-gestational age (LGA) or macrosomia. Data were combined in meta-analyses, and the quality of evidence for the effectiveness of the interventions was assessed in a GRADE approach. RESULTS Nineteen studies evaluating six types of interventions were included. Dietary counseling significantly reduced GDM incidence compared to standard care. None of the interventions was effective in lowering maternal fasting blood glucose. Low glycemic index (LGI) diet advice and an exercise program significantly reduced the risk of macrosomia. The quality of evidence for these outcomes was low. CONCLUSIONS The results indicate that there may be some benefits of dietary counseling, an LGI diet advice, or an exercise program. However, better-designed studies are required to generate higher quality evidence. At the moment, no strong conclusions can be drawn with regard to the best intervention for prevention of GDM.