Soft electronic devices that are capable of acquiring multichannel human body physiological signals noninvasively represent an important trend for healthcare monitoring. Combined strategies of materials design and advanced microfabrication on the system level present unique opportunities. In this presentation, I will discuss a rationally designed “island-bridge” matrix that allows hybridizing general classes of materials with soft substrates. Specifically, the hard components are integrated on the predefined distributed islands, and the wavy bridges will deform to absorb the externally applied stress. The results are fully functional systems that are rigid locally in the islands, but soft globally that places minimal constraint on the human body. Demonstrated prototypes include a multichannel health monitor that can sense local field potentials, temperature, strain, acceleration, and blood pressure in central arteries and veins. Integrate radios allow wirelessly transmitting the acquired data to the backend receiver. This platform technology holds profound implications for integrating a broad range of sensors, actuators, and circuit components, for monitoring, diagnosing, and even treating a broad range of health conditions.