Artificial electronic skin (e-skin), a network of mechanically flexible sensors which can wrap irregular surfaces conformally and quantify various stimuli sensitively, is potentially useful in healthcare monitoring and human machine interaction (HMI). However, although various approaches have mimicked structures and functions of the human skin, challenges remain for high density integration, super sensitivity and multi-functionality. Here we design a multimodal and comfortable skin-inspired active-matrix circuitry with high pixels density (> 100 /cm²) based on all two-dimensional materials, which exhibits excellent performance to detect both mechanical interactions and humidity variations. The ultrahigh sensitivity (> 400 and ~ 10⁴ for strain and humidity sensing respectively), long-term stability (> 1000 cycles) and rapid response time for every pixel can fulfill simultaneous multi-stimulus sensing. Accordingly, we constructed a respiratory monitor to realize healthcare monitoring through observing the human breath frequency, intensity and humidity in real time. Moreover, the multimodal e-skin breaks through shackles of contact sensor medium for HMI. Three-dimensional (3D) strain and humidity spatial mapping can reflect object location information even without contact, avoiding cross-infection of viruses effectively between the users during the COVID-19 pandemic. The reported e-skin can broaden applications for future healthcare and human-machine interactive devices.