A prerequisite for the development of hyperglycemia in diabetes is the inability of β-cells to secrete sufficient insulin to maintain glucose homeostasis. Current efforts to enhance β-cell function primarily focus on pathways that stimulate insulin release. However, little is known about the intracellular inhibitory mechanisms that terminate insulin secretion. Salt-inducible kinase 3 (SIK3) is a serine/threonine protein kinase that regulates multiple signaling pathways involved in metabolic regulation in response to hormonal and nutrient status changes. SIK3 is highly expressed in mouse pancreatic β-cells and is highly conserved in humans. Despite this, the role of SIK3 in regulating insulin secretion and β-cell biology has not been studied. In this talk, I will provide a detailed overview of the physiological roles of salt-inducible kinases in glycemic control and disease development, with a focus on the regulation of pancreatic β-cell biology and glucose metabolism by SIK3.