New circuit design techniques that accommodate lower supply voltages necessary for portable systems need to be integrated into the semiconductor intellectual property (IP) core. Systems that once worked at 3.3 V or 2.5 V now need to work at 1.8 V or lower, without causing any performance degradation. Also, the fluctuation of device characteristics caused by process variation in nanometer technologies is seen as design yield loss. The numerous parasitic effects induced by layouts, especially for high-performance and high-speed circuits, pose a problem for IC design. Lack of exact layout information during circuit sizing leads to long design iterations involving time-consuming runs of complex tools. There is a strong need for low-power, high-performance, parasitic-aware and process-variation-tolerant circuit design. This dissertation proposes methodologies and techniques to achieve variability, power, performance, and parasitic-aware circuit designs. Three approaches are proposed: the single iteration automatic approach, the hybrid Monte Carlo and design of experiments (DOE) approach, and the corner-based approach. Widely used mixed-signal circuits such as analog-to-digital converter (ADC), voltage controlled oscillator (VCO), voltage level converter and active pixel sensor (APS) have been designed at nanoscale complementary metal oxide semiconductor (CMOS) and subjected to the proposed methodologies. The effectiveness of the proposed methodologies has been demonstrated through exhaustive simulations. Apart from these methodologies, the application of dual-oxide and dual-threshold techniques at circuit level in order to minimize power and leakage is also explored.