Background and Purpose: The pharmacotherapy options in patients with gestational diabetes mellitus (GDM) are insulin or oral antihyperglycemic agents. Insulin is the preferred medication for treating hyperglycemia, but in recent years, metformin has been increasingly used in the treatment of GDM. Aim: The aim is to assess the efficacy of different treatments (insulin and metformin) in women with GDM. Methods: Screening for GDM was performed in 2422 pregnant women and revealed GDM in 119 women [75 g oral glucose tolerance test (OGTT) was performed at 24–28 weeks of gestation]. All patients started treatment at 24–29 weeks of gestation. The patients were divided into two groups (Gr.): Gr. 1 had 68 patients treated with diet and insulin therapy. Gr. 2 had 51 patients treated with diet and metformin. Results: In the 2nd trimester, HbA1c (%) levels for Gr. 1 and Gr. 2 were 6.7 (0.05) and 6.4 (0.6), respectively. By term, HbA1c levels statistically decreased in both groups, but we did not find a statistical difference between the groups. Women from Gr. 2 gained less weight compared to Gr. 1 (1.89 ± 3.88 vs. 4.53 ± 3.67 kg; P = 0.003). In Gr. 1, the percentage of preeclampsia was 2.9%, and in Gr. 2, 3.9% (P = 0.7773, OR - 1.33). We did not find a statistical difference between the groups. The incidence of preterm delivery before 37 weeks of gestation in Gr. 1 was lower than in Gr. 2 (P = 0.7311, OR - 1.33), and we also did not find a statistical difference between the groups. Perinatal mortality was observed in Gr. 1 - 1.4% and in Gr. 2 - 1.9% (P = 0.8402, OR - 1.33). In both groups, we observed a high percentage of cesarean section (Gr. 1 - 32.3% and Gr. 2 - 29.4% (P = 0.7651, OR -1.0909), but we did not find a statistical difference between the groups. In both groups, the percentage of macrosomia was high, despite good glycemic control maintained through pregnancies: 20.0% and 23.0% for Gr. 1 and Gr. 2, respectively (P = 0.9236, OR - 1.0256), and again no statistical difference was found between the groups. Percent of neonatal hypoglycemia was lower in Gr. 2 (1.9%) than in Gr. 1 (4.41%) (P = 0.9236, OR – 1.0256). Percent of respiratory distress syndrome was 2.94% and 3.92% for Gr. 1 and Gr. 2, respectively (P = 0.9694, OR - 0.9893), with no statistical difference between the groups. Conclusion: We did not find differences between patients treated with diet and insulin therapy and patients treated with diet and metformin. The percentage of preeclampsia, preterm delivery, macrosomia, and perinatal death were similar in both groups; only maternal weight gain was lower in the metformin group.