<p>Harnessing the collagenous structural hierarchy of leather is an intriguing strategy for developing the next-generation skin-friendly e-skins with integrated powerful multifunctional sensory capabilities. The current development of e-skins is significantly hindered by the limited breathability for the long-term wearability and the complexity of integrating multimodal sensors within confined device dimensions. The proteinous composition of leather is capable of providing e-skins with exceptional skin affinity, biocompatibility and water vapor permeability, thus guaranteeing the long-term wearing comfortability. The inherent hierarchical fibrous structure of leather combined with the unique reversible cross-scale deformation behaviors enables the in situ construction of highly sensitive microstructured sensors for realizing the miniaturization and integration of multimodal sensors within the constrained space of leather. As a consequence, the development of leather-based e-skins paves a new way for advancing leather industry from traditional manufacture to cutting-edge innovation.</p> Graphical Abstract <p></p>