Abstract: Objective To explore the effects of insulin detemir combined with insulin aspart on glycolipid metabolism and serum levels of neuregulin 4(NRG4), hepatocyte growth factor(HGF) and serum amyloid A(SAA) in patients with gestational diabetes mellitus(GDM). Methods A total of 200 patients with GDM admitted to No. 971 Hospital of the People's Liberation Army Navy from August 2022 to October 2024 were selected as the research subjects. All patients were divided into an observation group and a control group by random number table method, with 100 patients in each group. The control group was treated with insulin aspart combined with protamine human insulin, while the observation group was treated with insulin detemir combined with insulin aspart. Both groups were treated continuously for 8 weeks. The time to target of fasting plasma glucose(FPG) and 2-hour postprandial plasma glucose(2 hPG), as well as the insulin dosage at glycemic target, were compared between the two groups. Changes in FPG, 2 hPG, hemoglobin A1c(HbA1c), blood lipid indicators total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), and serum NRG4, HGF, and SAA were compared before treatment, at 4 weeks and 8 weeks after treatment, and the incidence of adverse maternal and neonatal outcomes was recorded. Results The time to target of FPG and 2 hPG in the observation group was shorter than that in the control group, and the insulin dosage at target was lower(P< 0.05); after 4 and 8 weeks of treatment, the levels of FPG, 2 hPG, HbA1c, TC, TG, LDL-C and SAA in the observation group were lower than those in the control group, while the serum NRG4 and HGF in the observation group were higher(P< 0.05). The incidences of preterm birth, postpartum hemorrhage and neonatal hypoglycemia in the observation group were lower(P< 0.05). Conclusion Insulin detemir combined with insulin aspart helps to improve glycolipid metabolism, regulate serum levels of NRG4, HGF and SAA, and reduce the incidence of preterm birth, postpartum hemorrhage, and neonatal hypoglycemia in GDM patients.