Conducting polymers (CPs) have gained attention as electrode materials in bioengineering mainly because of their mechanical softness compared to conventional inorganic materials. To achieve better performance and broaden bioelectronics applications, the surface modification of soft zwitterionic polymers with antifouling properties represents a facile approach to preventing unwanted nonspecific protein adsorption and improving biocompatibility. This feature article emphasizes the antifouling properties of zwitterionic CPs, accompanied by their molecular synthesis and surface modification methods and an analysis of the interfacial phenomenon. Herein, commonly used methods for zwitterionic functionalization on CPs are introduced, including the synthesis of zwitterionic moieties on CP molecules and postsurface modification, such as the grafting of zwitterionic polymer brushes. To analyze the chain conformation, the structure of bound water in the vicinity of zwitterionic CPs and biomolecule behavior, such as protein adsorption or cell adhesion, provide critical insights into the antifouling properties. Integrating these characterization techniques offers general guidelines and paves the way for designing new zwitterionic CPs for advanced biomedical applications. Recent advances in newly designed zwitterionic CP-based electrodes have demonstrated outstanding potential in modern biomedical applications.