This paper describes the functionalization of solid supported phospholipid bilayer with decellularized extracellular matrix (dECM) components, toward the development of biomimetic platforms that more closely mimic the cell surface environment. The dECM was obtained through a combination of chemical and enzymatic treatments of mouse adipose tissue that contains collagen, fibronectin, and glycosaminoglycans (GAGs). Using amine coupling chemistry, the dECM components were attached covalently to the surface of a supported lipid bilayer containing phospholipids with reactive carboxylic acid headgroups. The bilayer formation and the kinetics of subsequent dECM conjugation were monitored by quartz crystal microbalance with dissipation (QCM-D). Fluorescence recovery after photobleaching (FRAP) confirmed the fluidity of the membrane after functionalization with dECM. The resulting hybrid biomimetic interface supports the attachment and survival of the human hepatocyte Huh 7.5 and maintains the representative hepatocellular function. Importantly, the platform is suitable for monitoring the lateral organization and clustering of cell-binding ligands and growth factor receptors in the presence of the rich biochemical profile of tissue-derived ECM components.