In the presented work, the system and computer algorithms for low-frequency measurements with piezoresistive cantilever MEMS/NEMS devices are presented. The proposed solution enables low-frequency calibration and measurements in the presence of thermal drift. Applied analog and digital circuits solve a problem of a saturation of the response of a cantilever piezodetector. We also propose an algorithm, which enables further removal of the drift’s influence by the digital post-processing of a read signal. The results of 1/f noise measurements of a series of piezoresistive microcantilevers are presented. Shown 1/f noise spectra were measured and estimated by a data acquisition system utilizing digitally controlled electronics capable of removing the thermal drift. The results consistence with the theory confirms the validity of the presented approach.