CMOS biomedical systems have great potential to realize the vision of future healthcare service. In this dissertation, a complete overview of CMOS biomedical SoCs is first given. Introductions to the key building blocks, especially the readout part, and important design techniques are addressed. Then five wireless fully-integrated CMOS SoCs with different sensor readout/actuation circuits, which are designed and implemented for several biomedical applications covering biological, medical, and healthcare fields, are also completely introduced. First, two fully-integrated biosensor SoCs realized in TSMC 0.35 μm CMOS process are presented for label-free DNA molecule detection. One is designed based on cantilever sensor technology and oscillator-based self-calibrated readout circuit with high sensitivity (2 kHz/Ω), and it could detect < 0.02% of resistance variation (0.6 Ω) and achieve a limit of detection (LOD) of less than 1 pM. The other is designed based on polysilicon nanowire technology and chopper DDA-based readout circuit with features of low noise, high CMRR, and rail-to-rail input range. Its LOD is as low as 10 fM. The capability to distinguish one base-pair mismatched DNAs is also demonstrated. An implantable SoC integrating controller/actuation circuitry and 8 individually addressable drug reservoirs is also demonstrated for on-demand drug delivery. It is implemented by TSMC 0.35 μm CMOS technology and post-IC processing. Based on electrothermal activation technique, drug releases can be precisely controlled by wireless signals. Experiments show that the membrane failure occurs in 50 ms after activation current is applied. Implanted by minimally invasive surgery, this SoC can be used for the precise drug dosing of localized treatment, such as the cancer therapy, or the immediate medication to some emergent diseases, such as heart attack. To further develop a self-powered wireless biomedical platform able to address physical, chemical, and biological parameters, a highly adaptive multi-sensor SoC comprising four on-chip sensors and a smart wireless acquisition system is realized in TSMC 0.35 μm CMOS process. To intelligently process different types (C/R/I/V) of sensor signals, a linear (R2 = 0.999) and reconfigurable sensor readout is proposed. A two-input energy harvesting interface with conversion efficiency of 73 % is also integrated for long-term use. The entire SoC occupies die area of 11.25 mm2 and consumes only 942.9 μW. Experimental results show that four physiological parameters (temperature, glucose/protein concentration, and pH value) can be simultaneously monitored using this chip. Finally, a 473 μW wireless 16-channel biopotential acquisition SoC with UHF RF energy harvester is presented. It is fabricated in TSMC 0.18μm CMOS process with a die size of 4 mm × 3 mm. Using proposed PPM/OOK modulation, the power-consumption of the wireless transmitter can be dramatically reduced by 80%. A novel structure of AFE, which combines auto-zero technique and channel switching method to obtain both low-noise and low-power features, is also proposed in this work. During performing wireless transmission, this chip consumes only 473 μW at 1V supply voltage, and hence it is suitable for long-term wireless biopotential acquisition application.