Gestational diabetes mellitus (GDM) is a common pregnancy complication characterized by hyperglycemia in women without previously diagnosed diabetes. It is primarily caused by impaired glucose tolerance due to pancreatic β-cell dysfunction and chronic insulin resistance. Risk factors include overweight/obesity, advanced maternal age, and a family history of diabetes. GDM increases the risk of maternal cardiovascular disease and type 2 diabetes, as well as macrosomia and birth complications in the infant. Long-term risks include obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies globally, with rising numbers due to the obesity epidemic. While management strategies exist, there is no cure or effective prevention. Understanding the pathophysiology of GDM is crucial for developing new treatments. GDM is typically caused by β-cell dysfunction on a background of chronic insulin resistance. During pregnancy, insulin resistance increases, leading to hyperglycemia. β-cell dysfunction is exacerbated by insulin resistance, creating a cycle of hyperglycemia and further β-cell dysfunction. Insulin resistance is a key factor, with reduced insulin-stimulated glucose uptake contributing to hyperglycemia. Chronic insulin resistance is associated with impaired β-cell function and altered glucose metabolism. GDM is also linked to adipose tissue dysfunction, including reduced adipocyte differentiation and increased adipocyte size. Adipose tissue inflammation, characterized by increased macrophages and pro-inflammatory cytokines, contributes to insulin resistance. The liver plays a role in GDM through increased gluconeogenesis, while skeletal and cardiac muscle insulin resistance is a protective mechanism against metabolic stress. The placenta contributes to insulin resistance by secreting hormones and cytokines, and its function is affected by GDM. Placental transport of glucose, amino acids, and lipids is altered in GDM, contributing to fetal overgrowth. The gut microbiome may also play a role in GDM, with changes in microbial composition associated with increased risk. Oxidative stress and homocysteine levels are also implicated in GDM pathogenesis. The placenta is particularly sensitive to maternal hyperglycemia, contributing to fetal growth and macrosomia. Epigenetic and proteomic changes in the placenta are associated with GDM, though the mechanisms are not fully understood. Future research should focus on understanding the molecular mechanisms underlying GDM, including β-cell dysfunction and insulin resistance. Advances in genomics, epigenetics, and metabolomics may provide new insights into GDM pathogenesis and treatment. Understanding these mechanisms is essential for developing effective treatments and prevention strategies for GDM.Gestational diabetes mellitus (GDM) is a common pregnancy complication characterized by hyperglycemia in women without previously diagnosed diabetes. It is primarily caused by impaired glucose tolerance due to pancreatic β-cell dysfunction and chronic insulin resistance. Risk factors include overweight/obesity, advanced maternal age, and a family history of diabetes. GDM increases the risk of maternal cardiovascular disease and type 2 diabetes, as well as macrosomia and birth complications in the infant. Long-term risks include obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies globally, with rising numbers due to the obesity epidemic. While management strategies exist, there is no cure or effective prevention. Understanding the pathophysiology of GDM is crucial for developing new treatments. GDM is typically caused by β-cell dysfunction on a background of chronic insulin resistance. During pregnancy, insulin resistance increases, leading to hyperglycemia. β-cell dysfunction is exacerbated by insulin resistance, creating a cycle of hyperglycemia and further β-cell dysfunction. Insulin resistance is a key factor, with reduced insulin-stimulated glucose uptake contributing to hyperglycemia. Chronic insulin resistance is associated with impaired β-cell function and altered glucose metabolism. GDM is also linked to adipose tissue dysfunction, including reduced adipocyte differentiation and increased adipocyte size. Adipose tissue inflammation, characterized by increased macrophages and pro-inflammatory cytokines, contributes to insulin resistance. The liver plays a role in GDM through increased gluconeogenesis, while skeletal and cardiac muscle insulin resistance is a protective mechanism against metabolic stress. The placenta contributes to insulin resistance by secreting hormones and cytokines, and its function is affected by GDM. Placental transport of glucose, amino acids, and lipids is altered in GDM, contributing to fetal overgrowth. The gut microbiome may also play a role in GDM, with changes in microbial composition associated with increased risk. Oxidative stress and homocysteine levels are also implicated in GDM pathogenesis. The placenta is particularly sensitive to maternal hyperglycemia, contributing to fetal growth and macrosomia. Epigenetic and proteomic changes in the placenta are associated with GDM, though the mechanisms are not fully understood. Future research should focus on understanding the molecular mechanisms underlying GDM, including β-cell dysfunction and insulin resistance. Advances in genomics, epigenetics, and metabolomics may provide new insights into GDM pathogenesis and treatment. Understanding these mechanisms is essential for developing effective treatments and prevention strategies for GDM.