Islets of Langerhans are endocrine units of the pancreas. Local microenvironment of islets includes their immediate extracellular matrix and other molecules that surround islets within the exocrine pancreas. Transplantation of pancreatic islets, which is a promising method for treatment of type 1 diabetes, encounters several challenges including premature loss of grafted islets. The native islet extracellular matrix is disrupted during the process of enzymatic digestion of pancreas, which is required for isolation of islet from exocrine tissue. The lack of extracellular matrix then leads to a significant impairment of islet cell survival and function. This review outlines the significance of extracellular matrix in maintaining islet viability and integrity and summarizes the current body of knowledge regarding the role of different types of biocompatible extracellular matrices in improving islet cell viability and functionality in both in vitro and in vivo.