—A SystemC Multi-Domain Virtual Prototype (MDVP) framework provides multi-domain system integration of multi-electrode neural interface and a fast validation time, offering more efficient design process. In this paper, we propose efficient neuron cell, neuron tissue, and multi-channel neural interface front-end models implemented in a SystemC MDVP framework, which supports chemical, biological, and electrical domain modeling and simulation. The proposed model offers advantages for designers not only in reducing the design time, but also regarding the system integration. We make use of 8×16channel front-end recording circuits to implement a 128-channel time-multiplexed neural interface front-end model. These models are verified with realistic simulation settings and appropriate input signals. Keywords—SystemC MDVP, modeling, multi-channel, frontend neural interface