This paper presents a high precision CMOS weak current readout circuit. This circuit is capable of converting a weak current into a frequency signal for amperometric measurements with high precision and further delivering a 10-bit digital output. A fast stabilization-enhanced potentiostat has been proposed in the design, which is used to maintain a constant bias potential for amperometric biochemical sensors. A technique based on source voltage shifting that reduces the leakage current of the MOS transistor to the reverse diode leakage level at room temperature was employed in the circuit. The chip was fabricated in the 0.35 μm chartered CMOS process, with a single 3.3 V power supply. The interface circuit maintains a dynamic range of more than 100 dB. Currents from 1 pA to 300 nA can be detected with a maximum nonlinearity of 0.3% over the full scale.