Because of resistance to bio-macromolecular adhesion, antifouling hydrogels have attracted great attention in biomedical field. But traditional antifouling hydrogels made by hydrophilic polymers are always poor of mechanical properties. Herein, a new hybrid ionic-covalent cross-linked double network (DN) hydrogel was prepared by a simple one-pot method based on sodium alginate and the zwitterionic material carboxybetaine acrylamide (CBAA). The DN hydrogel has good mechanical properties, including high elastic modulus (0.28 MPa), high tensile strength (0.69 MPa), as well as good self-recovery capability. More importantly, the DN hydrogel is highly resistance to the adsorption of non-specific protein, cells, bacteria and algae, exhibiting an outstanding antifouling property. The in vitro and in vivo experiments prove that the DN hydrogel is highly biocompatible. This study provides a new strategy for the preparation of antifouling DN hydrogels with good mechanical properties for different needs, such as tissue scaffolds, wound dressings, implantable devices, and other fields.