Adhesive hydrogels have been widely studied as wound dressings due to their excellent biocompatibility and biological activity. However, most designed hydrogels still exist limitations including potentially toxic monomer, complex preparation process and non-degradable property. Here, a natural and degradable gelatin/casein hydrogel was prepared by enzymatic cross-linking. The hydrogel could adhere to tissue on-demand with the mediation of chitosan (CS) solution. It was found that the adhesion strength of hydrogel could be controlled by adjusting gelatin/casein ratio, EDC&NHS concentration, CS concentration, glycerol content and crosslinking degree. To further expand the applicability of hydrogels, the degradation and drug release rate of hydrogels could be modulated by changing transglutaminase (TG) concentration. Moreover, tetracycline hydrochloride (TH) was loaded into hydrogel as a drug model, which endowed hydrogel with good antibacterial properties. It was shown that the 0.03 % TH hydrogel had excellent blood compatibility and cell compatibility, and can promote the healing of infected wounds in mice. This research provides a new natural adhesive hydrogel for biomedical engineering field.