AIM: To investigate the role of ADIPOQ gene in gestational diabetes mellitus (GDM). METHODS: We genotyped single nucleotide polymorphisms (SNPs) rs266729 and rs1501299 within the ADIPOQ gene in a cohort of 1157 pregnant women of north Chinese Han ethnicity. This cohort comprised 560 pregnant women diagnosed with GDM and 597 pregnant women who exhibited normal oral glucose tolerance test at 24-28 weeks' gestation. All participants were recruited from the Department of Obstetrics and Gynecology at the Second Affiliated Hospital of Harbin Medical University. Additionally, we used conventional bioinformatics analysis methods to conduct multi-omics analysis (transcriptome, epigenome, and single-cell level) of ADIPOQ-regulated GDM. RESULTS: The systolic blood flow velocity/diastolic blood flow velocity (S/D) ratio of the umbilical artery in GDM patients with CC genotype of rs266729 and GG genotype of rs1501299 was higher than control. Single-cell analysis suggested that ADIPOQ was expressed in extravillous trophoblast (EVT), T cell, monocytes, myelocyte, NK cell and syncytiotrophoblast (SCT). Functional enrichment analysis showed ADIPOQ gene was associated with response to nutrient levels, fat cell differentiation. CONCLUSION: The findings of our study indicate a correlation between SNPs of ADIPOQ in GDM patients, and ADIPOQ is involved in the transcriptional regulation of GDM.