Integrated circuits fabricated by advanced and high-yield CMOS processes feature various exclusive advantages compared to conventional bulky implementations using discrete components. Benefiting from device miniaturization, systems with unprecedented functionality and significantly improved performance have reshaped numerous fields that exploit sensing and communication techniques. In this thesis, four energy-efficient CMOS and silicon photonic microsystems enabled by both architecture-level and circuit-level low-power design techniques are presented, which cover different topics ranging from implantable medical devices to high-speed optical transceivers, and various signal frequency regimes from sub-kHz to near-infrared.First, an analog SoC for real-time signal processing of neural action potentials is implemented by integrating a low-noise neural recording front-end with an unsupervised spike sorting classifier. A hardware-optimized, K-means based algorithm is proposed to effectively eliminate duplicate clusters, which is realized by a clock-less and ADC-less architecture. Second, a somatosensory feedback system, composed of wireless body channel transceivers and implantable sensor nodes, is developed to close the control loop for bi-directional limb reanimation. A fully wireless sensor interface IC is implemented to form an artificial mechanoreceptor with a MEMS capacitive force sensor. The self-interference issue, which is frequently encountered in sensor systems requiring concurrent power and data links, is resolved through frequency conversion performed by a mixer-first topology. An injection-locked relaxation oscillator topology is utilized to perform energy-efficient frequency-shift keying demodulation. An ultra-low power tactile sensing network with individual accessibility and programmability is also presented. Third, leveraging the seamless, micron-scale interconnection between photonics and electronics on a monolithic CMOS-silicon photonics platform, an optical PAM4 receiver with superior power and area efficiency is proposed. Enabled by its outstanding scalability, 32 receiver channels are integrated on the same die to demonstrate a wavelength-division multiplexing system with an aggregate data-rate beyond terabit per second. Finally, an electronic-photonic lab-on-chip is realized by integrating all the essential blocks for a self-contained near-infrared sensing system. Utilizing on-chip optical energy harvester and optical transmitter/receiver, a dual fiber interface is employed to achieve long-reach and low-cost optical interconnects.