Strong nonspecific protein/cell adhesion on conducting polymer (CP)-based bioelectronic devices can cause an increase in the impedance or the malfunction of the devices. Incorporating oligo(ethylene glycol) or zwitterionic functionalities with CPs has demonstrated superior performance in the reduction of nonspecific adhesion. However, there is no report on the evaluation of the antifouling stability of oligo(ethylene glycol) and zwitterion-functionalized CPs under electrical stimulation as a simulation of the real situation of device operation. Moreover, there is a lack of understanding of the correlation between the molecular structure of antifouling CPs and the antifouling and electrochemical stabilities of the CP-based electrodes. To address the aforementioned issue, we fabricated a platform with antifouling poly(3,4-ethylenedioxythiophene) (PEDOT) featuring tri(ethylene glycol), tetra(ethylene glycol), sulfobetaine, or phosphorylcholine (PEDOT-PC) to evaluate the stability of the antifouling/electrochemical properties of antifouling PEDOTs before and after electrical stimulation. The results reveal that the PEDOT-PC electrode not only exhibits good electrochemical stability, low impedance, and small voltage excursion, but also shows excellent resistance toward proteins and HAPI microglial cells, as a cell model of inflammation, after the electrical stimulation. The stable antifouling/electrochemical properties of zwitterionic PEDOT-PC may aid its diverse applications in bioelectronic devices in the future.