To explore the correlation between the hypothyroidism, metabolic changes, and weight gain of pregnant women and their risk of gestational diabetes mellitus (GDM) occurrence. Methods: 331 pregnant women with GDM screened in the obstetric clinic from January 2019 to December 2021 were collected in study group retrospectively, and 340 pregnant women with normal glucose tolerance during the same period were selected in control group. The abnormal rate of thyrotropic stimulating hormone (TSH) level, the hypothyroidism rate, the positive rate of thyroid peroxidase antibody (TPOAb), and the serum free triiodothyronine (FT3) and free thyroxine (FT4) levels of the women were compared between the two groups. The differences of the individual physiological indicators and blood glucose and lipid indicators of the women during pregnancy were statistically analyzed. The correlation between the GDM occurrence of the women and their above indicators was analyzed by logistic regression model. Results: The proportions of the pregnancy weight gain and the family history of diabetes of the women in the study group were significantly higher than those of the women in the control group (all P＜0.05). There were no significant differences in the age, the pre-pregnancy body mass index, the proportion of primipara, and the values of systolic blood pressure and diastolic blood pressure of the women between the two groups (P>0.05). The proportions of the increase of TSH level, the hypothyroidism, and the TPOAb positive of the women in the study group during the first trimester of pregnancy were significantly higher than those of the women in the control group (all P＜0.05). There were no significant differences in the serum FT3 and FT4 levels of the women between the two groups (P>0.05). The levels of fasting blood glucose, glycated hemoglobin, triglyceride (TG), and low density lipoprotein of the women in the study group were significantly higher than those of the women in the control group (all P＜0.05). There were no significant differences in the serum total cholesterol and high density lipoprotein levels of the women between the two groups (P>0.05). Logistic regression analysis showed that pregnancy weight gain, the family history of diabetes, the hypothyroidism, and the high serum TG level of the women were the independent risk factors of their GDM occurrence (P＜0.05). Conclusion: The level of TSH of the women with GDM increases significantly during the first trimester of pregnancy. The more weight gain during pregnancy, the family history of diabetes, the hypothyroidism, and the high serum TG level of the women all are the independent risk factors of their GDM occurrence.