A simple and new CMOS potentiostat circuit for amperometric sensor is described. To maintain a constant potential between the reference and working electrodes, only one differential difference amplifier (DDA) is needed in proposed design, while conventional potentiosatat requires at least 2 operational amplifiers and 2 resistors, or more than 3 operational amplifiers and 4 resistors for low voltage CMOS integrated potentiostat. The DDA with rail-to-rail design not only enables the full range operation to supply voltage but also provides simple potentiostat system with small hardwares and low power consumption.