Hydrogels are hydrophilic polymeric networks capable of absorbing large amounts of water or biological fluids. Hydrogel is a promising biomaterial in medicine due to its high water content and similar structure to biological soft tissues. However, traditional hydrogels are soft and brittle, lacking the proper mechanical properties to model the biological soft tissues and also limiting their biomedical applications. Double-network hydrogels (DN hydrogels) are recently developed to improve the mechanical properties (e.g., toughness and extensibility) and expand the biomedical applications of hydrogels through the selection of polymers and the design of crosslinking network. Here, we will discuss the preparation, crosslinking network and biomedical applications of DN hydrogels.