A fully differential CMOS analog front-end circuit for electrochemical sensing is presented. Its first stage is based on a differential transimpedance amplifier (TIA) with an input common-mode feedback to maintain the potentials at the differential working electrodes. The differential output of the first stage is further amplified at the second stage to resolve a smaller range of current differences down to less than 100 fA. The integration capacitor in the first stage and the gain of the second stage are programmable to cover a wide range of the input current ranges up to a range of μA. The proposed potentiostat incorporates two ADC stages, one for each stage. While the outputs of the first stage are compared with a threshold voltage, the whole integration time for both the currents is converted to digital by counters. When difference between the two inputs is too small to be resolved by this ADC, the second stage now becomes a dual-slope ADC to quantize the amplified difference. The ADC in the second stage incorporates a charge/discharge current source, which allows a time-domain measurement of the amplified signal. This method avoids the use of a separate ADC stage, which will consume additional power and area. The proposed potentiostat circuit is designed in 180nm CMOS SOI process technology. Simulation results show that this architecture can accurately measure the differential input current from 1 pA to 1 μA. The minimum input referred integrated current noise in 1 Hz to 10 kHz bandwidth is less than 100 fA with power consumption of 15 μA from ±1-V supply. This fully differential design is adequate to be integrated in an implantable amperometric electrochemical sensing device with low area and power requirements while offering robustness to background current variations.