Background Transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism has been shown to display a significant association with gestational diabetes mellitus (GDM). But the effects of TCF7L2 rs7903146 on glucose and lipid metabolism are not clear. Objective The purpose of this study was to assess the role of TCF7L2 rs7903146 genotypes on glycolipid metabolism in GDM. Methods In total, 484 individuals (239 in GDM group and 245 in control group) were included in the final analysis from January 2015 to February 2022. Their baseline demographics, plasma lipid concentration in the first trimester and third trimester, blood glucose values of the OGTT during gestational 24–28 weeks, glycosylated hemoglobin, fasting plasma glucose and fasting insulin in third trimester, 1 min Apgar scores, 5 min Apgar scores, glucose values of cord blood, and umbilical artery pH were collected. TCF7L2 rs7903146 genotypes were analyzed by polymerase chain reaction-Sanger sequencing. Results The frequencies of TCF7L2 rs7903146 genotype were found to have no significant differences between the two groups; however, the plasma lipid concentrations during the first trimester were higher in GDM group than control group. In GDM group, women carried the risk allele (T) in TCF7L2 rs7903146 displayed the significantly higher glucose values at 1-h during OGTT, and the higher TG and lower fasting insulin levels than those in non-carriers. Conclusion Our results indicate that the risk allele (T) in TCF7L2 rs7903146 plays an important role in the abnormality of glucose and lipid metabolism in GDM women. For the risk allele(T) carriers of TCF7L2 rs7903146, low-fat and low-sugar diets, exercise interventions can be carried out at an early stage, and insulin therapy should be considered when their blood glucose were inadequately controlled.