Understanding the organisation and role of the extracellular matrix (ECM) in islets of Langerhans is critical for maintaining pancreatic β-cells, and to recognise and revert the physiopathology of diabetes. Indeed, integrin-mediated adhesion signalling in response to the pancreatic ECM plays crucial roles in β-cell survival and insulin secretion, two major functions, which are affected in diabetes. Here, we would like to present an update on the major components of the pancreatic ECM, their role during integrin-mediated cell-matrix adhesions and how they are affected during diabetes. To treat diabetes, a promising approach consists in replacing β-cells by transplantation. However, efficiency is low, because β-cells suffer of anoikis, due to enzymatic digestion of the pancreatic ECM, which affects the survival of insulin-secreting β-cells. The strategy of adding ECM components during transplantation, to reproduce the pancreatic microenvironment, is a challenging task, as many of the regulatory mechanisms that control ECM deposition and turnover are not sufficiently understood. A better comprehension of the impact of the ECM on the adhesion and integrin-dependent signalling in β-cells is primordial to improve the healthy state of islets to prevent the onset of diabetes as well as for enhancing the efficiency of the islet transplantation therapy.