Electronic skins (E-skins) capable of biomechanical/bioelectrical signal acquisition are intensively pursued for human-centered healthcare of daily life. For practical use, it is highly desired, yet challenging, to mass-produce E-skins that are soft and breathable for wearing comfort, skin-adhesive for robust signal acquisition, multi-signal sensing for enhanced healthcare data. Herein, a scalable fabrication strategy for a bioinspired E-skin (SPRABE-skin) with a multi-layered architecture is reported that integrates skin-like softness, self-protection, self-adhesion, breathability, and bimodal sensing in a single patch. The fibrous thermoplastic polyurethane (TPU) scaffold endows the SPRABE-skin with tissue-like softness (Young's modulus of 3.36 MPa) and stretchability, good permeability to water vapor, and self-protection against adverse loading events. A strain sensing layer composed of MXene-carbon nanotubes@TPU (MXene-CNT@TPU) composition exhibits ultra-high sensitivity in a wide sensing range (gauge factor at strain of 485% reaches 63 494). An electrode layer made of MXene-waterborne polyurethane (MXene-WPU) provides a highly adhesive electrode-skin interface, which enables the acquisition of biopotentials, such as electrocardiograph (ECG), electromyograph (EMG), electroencephalo-graph (EEG), with improved fidelity even under various dynamic interferences. Finally, a SPRABE-skin based human-centered healthcare system is demonstrated that realizes the wireless, long-duration, and dynamic monitoring of ECG and running activities.