Fetuin-A (FetA) is a 64-kDa glycoprotein that is secreted from both the liver and adipose tissue. Circulating FetA is elevated in obesity and related disorders including type 2 diabetes mellitus, nonalcoholic fatty liver disease and the metabolic syndrome; and a FetA-related parameter, caliciprotein particle, is highly relevant to vascular calcification in overweight/obese patients with chronic kidney disease. FetA level is also associated with impaired insulin sensitivity and glucose tolerance. Accumulating evidence suggests that elevated FetA level causes impaired glycemic control, as FetA has been implicated in impairment of insulin receptor signaling, toll-like receptor 4 activation, macrophage migration and polarization, adipocyte dysfunction, hepatocyte triacylglycerol accumulation and liver inflammation and fibrosis. Weight loss, aerobic exercise, metformin and pioglitazone have each been shown to be effective for reducing FetA level.