〔Abstract〕 Objective To investigate the efficacy of metformin combined with insulin aspartic in the treatment of gestational diabetes mellitus and the effects on adiponectin (APN), fatty acid binding protein 4 (FABP4) and SRY box transcription factor 4 (SOX4) . Methods A total of 90 patients with gestational diabetes mellitus diagnosed and treated in the Third Affiliated Hospital of Zhengzhou University from January 2020 to June 2022 were selected and divided into metformin combined with insulin aspartate treatment group (observation group) and insulin aspartate treatment group (control group) according to treatment methods, with 45 cases in each group. The differences of pregnancy outcome, blood glucose index, insulin resistance index (HOMA-IR), APN, FABP4 and SOX4 between the two groups were compared. Results The incidences of premature delivery, cesarean section, abnormal amniotic fluid, postpartum hemorrhage and postpartum infection in the observation group was lower than those in the control group, and the differences were statistically significant (P < 0.05). The incidences of neonatal weight abnormality, hypoglycemia, neonatal jaundice, respiratory distress and death in the observation group were lower than those in the control group, and the differences were statistically significant (P < 0.05). The level of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), 2h postprandial blood glucose (2h PG) and HOMA-IR in the observation group after treatment were lower than those in the control group, and the differences were statistically significant (P < 0.05). After treatment, The level of APN in the observation group was higher than that in the control group, the levels of FABP4 and SOX4 were lower than those in the control group, and the differences were statistically significant (P < 0.05). Conclusion Metformin combined with insulin aspartate can improve the blood sugar and insulin resistance status of gestational diabetes patients, and improve the pregnancy outcome of gestational diabetes patients, and its efficacy is higher than that of insulin aspartate alone.