In the highly sensitive detection field, charge-sensitive amplifier is widely used in the preamplifier of detectors, however, the high voltage applied to these detectors (such as CZT nuclear detector) often make serious noise, which may influence the sensitivity of the detector. Despite the traditional passive filter circuit to eliminate the noise of the power, but if the power supply accuracy isn’t high enough and the passive circuit eliminate the power supply noise is incomplete. The noise still may affect the performance of the final system. According to the need of nuclear detection and photoelectric detection, a kind of differential JFET charge-sensitive preamplifier is proposed in this paper, which eliminates the power-supply noise and Johnson noise of bias resistance. First, theoretical analysis of the traditional JFET circuit is proved and simulation of the JFET circuit is performed with ORCAD software, which prove that power-supply noise effect the preamplifier. Next, simulation of the innovative circuit is performed with ORCAD software. Finally, the fabricated circuit board is tested with avalanche photo diode (APD). It is shown that the charge-sensitive preamplifier with differential JFET input can significantly eliminate the power-supply noise and Johnson noise of resistance (both low frequency and high frequency) and realize a high sensitivity.