Objective To investigate the methylation levels of the HIF?3α gene， as well as the expression of HIF?3α mRNA and DDIT4 mRNA in peripheral blood samples from pregnant women with gestational diabetes mellitus （GDM）， and their association with pregnancy outcomes， aiming to provide insights for pregnancy monitoring and clinical diagnosis and treatment of GDM patients， thereby mitigating the risk of adverse pregnancy outcomes. Methods From March 2023 to March 2024， a total of 80 pregnant women with GDM were randomly selected at the Affiliated Hospital of Xuzhou Medical University. They were divided into two groups based on glycemic control： GDM1 （n = 40） representing good glycemic control and GDM2 （n = 40） representing poor glycemic control. Additionally， a control group consisting of 40 pregnant women without any pregnancy complications or comorbidities was included. Methylation-specific PCR was employed to determine the rate of HIF-3α methylation， while quantitative real-time PCR was used to assess the expressions of HIF-3α mRNA and DDIT4 mRNA. Adverse pregnancy outcomes were recorded across all three groups， and correlations between HIF-3α mRNA， DDIT4 mRNA， and various adverse pregnancy outcomes were analyzed using logistic regression analysis. Results Prior to pregnancy， GDM1 and GDM2 groups exhibited higher levels of FPG， HbA_1c， TC， TG， LDL-C， FINS and HOMA-IR （P < 0.05）， as well as lower levels of HOMA-β compared to the control group （P < 0.05）. The incidence of adverse pregnancy outcomes was also higher in both GDM groups than in the control group； this difference was significant for GDM2 （P < 0.05） but not for GDM1 （P > 0.05）. Furthermore， methylation rates of the HIF-3α gene were higher in both GDM groups compared to controls while expression levels of HIF-3α and DDIT4 mRNA were lower； these differences were significant for the GDM2 group versus controls （P < 0.05） but not for the GDM1 group versus controls （P > 0.05）. Finally， all adverse pregnancy outcomes among women with gestational diabetes mellitus showed a negative correlation with expression levels of both HIF-3α and DDIT4 mRNA （r < 0，P < 0.05）； moreover， these two mRNAs served as protective factors against such outcomes occurring（OR < 1，P < 0.05）. Conclusion The higher methylation rate of HIF-3α and the decreased expression of HIF-3α and DDIT4 genes are associated with the development of GDM and may serve as significant factors contributing to adverse pregnancy outcomes.