It has been shown that women who gained an excessive weight during pregnancy had an increase in long-term BMI compared with those without an excessive weight gain. Several studies have demonstrated that some polymorphisms of the glucocorticoid receptor (GR) gene may influence body composition and metabolic parameters. In the present study, we wanted to explore whether any association could exist between the BclI, N363S and ER22/23EK polymorphisms of the GR gene and the weight gain during pregnancy. We found that the allelic frequencies of the BclI, N363S and ER22/23EK polymorphisms in 300 women with uncomplicated pregnancies were similar to those measured in healthy Hungarian population. None of the three polymorphisms associated with body weight or BMI at the 1st trimester of pregnancy or before delivery. However, a significantly lower weight gain (p = 0.044) and consequently lower increase of BMI during pregnancy (p = 0.044) was observed in heterozygous carriers of the ER22/23EK polymorphism. These results support a protective role of the ER22/23EK polymorphism against an excessive weight gain and excessive increase of BMI during uncomplicated pregnancy.