In this paper, an energy-efficient and low-noise 16-channel analog front-end (AFE) circuitry is proposed for acquisition of electrophysiological signals. This fully integrated front-end circuit comprises two differential difference amplifiers (DDAs) and DC offset rejection components. Additionally, the DDA is designed using a double input Gm-stage and a class-AB output for achieving high common-mode rejection ratio (CMRR), low-noise and energy efficiency. The 16-channel AFE with analog-to-digital converters (ADCs) is implemented in TSMC 0.18μm CMOS process. The measurement results show that the AFE can realize 60.3dB gain with only 20.67μW for each channel. The bandwidth of the AFE is from 2.32Hz to 6.61kHz. Furthermore, the total input referred noise and noise efficiency factor (NEF) are 0.826μVrms and 2.78 only within the target frequency range of 0.1Hz to kHz, respectively.