These data were generated to investigate the association and functional analysis of angiotensin-converting enzyme 2 genetic variants with the pathogenesis of Gestational diabetes mellitus (GDM). This study conducted a case-control study involving 569 GDM patients and 735 healthy pregnant women to explore the associations between candidate variants in the ACE2 gene variants and the pathogenesis of GDM. This study collected clinical samples and data, and used logistic regression, false positive report rate, multi factor dimension reduction, functional analysis and other analysis methods to process the research data. Potential functional ACE2 gene variants (rs2106809 A>G, rs6632677 G>C, and rs2074192 C>T) were selected and genotyped using kompetitive allele-specific PCR. The strength of the associations between the studied genetic variants and the risk of GDM were evaluated using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Finally, ACE2 gene variants are significantly associated with the risk of GDM via gene-gene and gene-environment combination. The rs2074192 C > T affects the splicing of ACE2 gene, which may be a potential mechanism leading to the altered susceptibility of individual female during pregnancy in Guilin to GDM