In this article, an efficient differential voltage amplifier scheme for interfacing piezoelectric sensors that is insensitive to cable parasitic capacitance and immune to common mode interference (CMI) is presented. The scheme is beneficial for improving the sensitivity and signal-to-noise ratio (SNR) performance of high piezoelectric voltage constant (piezopolymer) piezo-sensor-based applications involving long cables between the piezo-sensor and electronics. In many piezo-sensor applications operating in harsh environments, the piezo-sensor and electronics need to be separated using long cables. The cable introduces signal loading, the triboelectric effect, and the picking up of external interference, resulting in poor sensitivity and SNR performance. Piezopolymer-based sensors e.g., polyvinylidene fluoride (PVDF) have high voltage sensitivity compared to charge sensitivity, which results in improved sensitivity performance if a voltage amplifier is used instead of a charge amplifier for interfacing these sensors. Hence, an enhanced differential voltage amplifier scheme insensitive to cable parasitic capacitance and immune to triboelectric effect and CMI is presented in this article. The proposed scheme has been simulated using LTspice, and a prototype has been implemented. The performance has been evaluated in the presence of cable parasitic capacitance and common-mode interference. The experimental result shows that the sensitivity is improved by 4.55 dB in comparison with a normal differential amplifier when a 5-m dual-core cable is used to connect a piezo-sensor (Airmar AT200). The proposed differential scheme improved the rejection of CMI by 18 dB compared with the single-ended configuration of the scheme.