AIM: Gestational diabetes, characterized by impaired glucose tolerance occurring or diagnosed during pregnancy, is a significant public health concern. When lifestyle and dietary measures fail (30 % of women), insulin is the standard treatment. Oral antidiabetic agents, such as metformin (Glucophage) and glibenclamide, could provide a promising alternative. The aim here was to evaluate the effectiveness and safety of these treatments in gestational diabetes. METHODS: This study is based on a systematic literature review. A keyword search for "metformin (Glucophage)," "glibenclamide," "pregnancy," and "gestational diabetes" was conducted in the PubMed and Google Scholar databases from 2013 to 2023. RESULTS: A total of 45 studies were selected and analyzed. metformin (Glucophage) appears to offer a combination of effectiveness in glycemic control and maternal and neonatal safety. Compared to insulin, it reduces maternal weight gain, lowers maternal hypoglycemia rates, and shows a tendency to reduce gestational hypertension and preeclampsia. Additionally, infants born to mothers on metformin (Glucophage) are less likely to be macrosomic, experience fewer neonatal hypoglycemic episodes, and require fewer admissions to intensive care units. On the other hand, glibenclamide seems effective in glycemic control but is associated with higher rates of macrosomia and neonatal hypoglycemia. CONCLUSION: Metformin (Glucophage) appears to be a promising alternative to insulin for treating gestational diabetes, while uncertainties remain regarding the safety of glibenclamide.