Zwitterionic polymers have both anion and cation groups in one molecular chain. They include several types of polymers such as phosphorylcholine-, sulphobetaine-, carboxyl betaine-, and mixed-charge polymer, according to the different macromolecular structures. They can be cationic or anionic polyelectrolyte by adjusting the pH values in aqueous solutions. They also have a particular anti-polyelectrolyte behavior. Moreover, they have been endowed with lots of other excellent properties, such as strong hydrophilicity, good thermo and chemical stabilities, excellent biocompatibility, and antifouling property. Various zwitterionic polymer materials have been successfully applied in many fields. In this review, the recent progress in antifouling materials, drug delivery carries, and detection and separation materials are summarized. Especially, the developments in the mechanism of protein resistance adsorption are highlighted. The hydration of zwitterionic polymers plays an important role in resisting proteins adsorption, which dominatingly depends on the chemical structures of zwitterionic polymers, such as polymer density, cationic and anionic species and their space length, and charge arrangement. Just based on the properties of protein resistance adsorption and polyelectrolyte, zwitterionic polymers are also used as a block in copolymers or gels to prepare nanocarriers for drug delivery. In preparation of detection and separation materials, the research progress of polymer monolithic columns are particularly summarized, for their excellent stability for resisting a long-term solvent washing and high temperature. In addition, the development perspectives of zwitterionic polymers are also discussed.