Chemiresistor (CR) sensors and sensor arrays coated with thiolate-monolayer-protected gold nanoparticle (MPN) interfaces show great promise as detectors in gas-chromatographic microsystems with applications in biomedical and environmental analysis including breath biomarkers of disease. This paper describes a new readout circuit that overcomes the wide range of baseline resistances and drift in baseline values inherent to MPN-coated CRs to achieve a 57 ppm readout resolution. The 0.5-mum CMOS circuit operates at 5 V and provides a response resolution of 74 muV. It can cancel baseline voltages from 0.3 to 4.3 V with an accuracy of 4.2 mV and can track and compensate for drifts up to 30 mV/min. Performance was verified with MPN-coated CRs, where drift was measured and effectively cancelled. The circuit topology and size support an on-chip MPN-coated CR sensor array.