Background The glucose intolerance developed during pregnancy is called gestational diabetes mellitus (GDM). GDM has become a severe risk for the health of both mother and baby. Astragaloside IV (AS-IV) is the dominant active component in Astragalus membranaceus and has been reported to have anti-inflammation and immune-regulation function. We aimed to demonstrate the function of AS-IV in the therapy of GDM and the molecular mechanism in this process. Methods C57BL/KsJ-Lepdb/+ female mice were used as GDM model. The mRNA levels of relative genes in this research were detected by qRT-PCR. The protein levels of relative genes were analyzed by western blot. Serum lipid level was measured by ILab Chemistry Analyzer 300 PLUS. Results Glucose, insulin, and lipid profile levels in GDM mice model were decreased by AS-IV treatment. AS-IV down-regulated the expression of inflammatory genes and up-regulated the expressions of antioxidant genes in GDM mice model. AS-IV treatment reduced cAMP accumulation in liver and reduced hepatic gluconeogenesis in GDM mice. Conclusion This study demonstrated that AS-IV treatment has an effective therapeutic function of GDM in mice model through the regulation of cAMP accumulation and hepatic gluconeogenesis.