Zwitterionic polymers have hydrophilic anion and cation groups simultaneously, which make them highly hydrated and render them unique biological antifouling property, i.e., those polymers can resist nonspecific protein adsorption, bacterial adhesion, and biofilm formation. Such character makes them increasingly applied in a wide range of biological and medical related fields recently. The widely accepted antifouling mechanisms, steric effects and hydration theory, are briefly introduced. Based on the biological antifouling character, zwitterionic polymers can be used in antifouling coatings of medical devices, antimicrobial coatings, anticoagulation coatings, biomedical diagnosis, drug delivery in vivo, gene delivery carriers, membrane separation and marine coatings. The article mainly reviews the progress of those applications. Finally, issues existed in these applications are also discussed and the perspective of these applications are put forward.