Nanocellulose-based hydrogels have shown promising potential in the field of biomedicine. They have been explored in biomedical applications, such as 3D cell culture, tissue engineering, diagnostics, drug delivery, and the separation of biomolecules and cells. An important property of hydrogels used in biomedicine is their ability to mimic the physical and biochemical environment in the human body or other biological systems. The high water content of hydrogels enables properties similar to those of the human body, and the modification of cellulose provides possibilities for enhancing properties and controlling biological interactions.1 One common drawback of materials used in biomedicine is the immune response and nonspecific protein adsorption. Nonspecific protein adsorption is the accumulation of proteins on the surface of the foreign material, this affects the effect of, e.g., the implant or drug delivery and can lead to a foreign body immune response. A group of materials that have shown promising antifouling properties, i.e., resist protein adsorption, and have gained attention in both the biomedical and engineering fields in recent years are zwitterionic materials. These materials include both anionic and cationic moieties, giving them an overall neutral charge when the two moieties are equally distributed in the material. This neutral charge contributes to a strong hydration effect and shows antifouling characteristics.2,3This work focused on the development of a synthesis method for zwitterionic cellulose and the preparation of a zwitterionic hydrogel. Therefore, zwitterionic groups sulfobetaine and carboxybetaine were synthesized, characterized, and grafted onto cellulose to synthesize zwitterionic nanocellulose hydrogels. The possibility for multiple cellulose functionalization in the same material was explored, with methacrylated cellulose4 further modified zwitterionically to endow the material with photocurable and zwitterionic functionality.