As a carbon nanomaterial, graphene exhibits the superior mechanical, electrical and thermal properties, indicating an enormous application potential in the field of flexible electronic devices. In flexible devices, interfacial mechanical performance between graphene and flexible substrate can determine the reliability of devices performance. This review represented recent development on the interfacial mechanical performance of graphene/flexible substrate, i.e., experimental technology (by Raman spectroscopy, atomic force microscopy and pressurized blister test) and theoretical calculation model (shear-lag theory, nonlinear shear-lag analysis, bilinear cohesive law and two-dimensional nonlinear shear-lag mode). In addition, the relevant applications and difficulties of flexible graphene devices based on its interfacial mechanical research were also introduced. Finally, the future research and application were prospected.