The main topic of this thesis is the development of a chemical microsystem based on integration of a silicon-based resonant microsensor and a CMOS ASIC for portable sensing applications. Cantilever and disk-shape microresonators have been used as mass-sensitive sensors. Based on the characteristics of the microresonators, CMOS integrated interface and control electronics have been implemented. The CMOS ASIC utilizes the self-oscillation method, which incorporates the microresonator in an amplifying feedback loop as the frequency determining element. In this manner, the ASIC includes a main feedback loop to sustain oscillation at or close to the fundamental resonance frequency of the microresonator. For stable oscillation, an automatic gain control loop regulates the oscillation amplitude by controlling the gain of the main feedback loop. In addition, an automatic phase control loop has been included to adjust the phase of the main feedback loop to ensure an operating point as close as possible to the resonance frequency, resulting in improved frequency stability. The CMOS chip has been interfaced to cantilever and disk-shape microresonators and short-term frequency stabilities as low as 3.4×10-8 in air have been obtained with a 1 sec gate time. The performance of the implemented microsystem as a chemical sensor has been evaluated experimentally with microresonators coated with chemically sensitive polymer films. With a gas-phase chemical measurement setup constructed in this work, chemical measurements have been performed and different concentrations of VOCs, such as benzene, toluene and m-xylene have been detected with limits of detection of 5.3 ppm, 1.2 ppm and 0.35 ppm, respectively. To improve the long-term stability in monitoring applications with slowly changing analyte signatures, a method to compensate for frequency drift caused by environmental disturbances has been implemented on the CMOS chip. This method uses a controlled stiffness modulation generated by a frequency drift compensation circuit to track the changes in the resonator's Q-factor in response to variations in the environmental conditions. The measured Q-factor is then used to compensate for the frequency drift using an initial calibration step. The feasibility of the proposed method has been verified experimentally by compensating for temperature-induced frequency drift during gas-phase chemical measurements.