A novel fully differential difference CMOS potentiostat suitable for neurotransmitter sensing is presented. The described architecture relies on a fully differential difference amplifier (FDDA) circuit to detect a wide range of reduction-oxidation currents, while exhibiting low-power consumption and low-noise operation. This is made possible thanks to the fully differential feature of the FDDA, which allows to increase the source voltage swing without the need for additional dedicated circuitry. The FDDA also reduces the number of amplifiers and passive elements in the potentiostat design, which lowers the overall power consumption and noise. The proposed potentiostat was fabricated in 0.18 µm CMOS, with 1.8 V supply voltage. The device achieved 5 µA sensitivity and 0.99 linearity. The input-referred noise was 6.9 µV rms and the flicker noise was negligible. The total power consumption was under 55 µW. The complete system was assembled on a 20 mm × 20 mm platform that includes the potentiostat chip, the electrode terminals and an instrumentation amplifier for redox current buffering, once converted to a voltage by a series resistor. the chip dimensions were 1 mm × 0.5 mm and the other PCB components were off-chip resistors, capacitors and amplifiers for data acquisition. The system was successfully tested with ferricyanide, a stable electroactive compound, and validated with dopamine, a popular neurotransmitter.