Summary: Dental implants make it possible to replace teeth in more sophisticated ways. Nevertheless, peri-implantitis is one of the leading causes of implant failure, which can be avoided with proper soft tissue sealing. The aim of this study was to achieve the promotion of the synthesis of peri-implant epithelial hemidesmosome through Histatin 1 and porcine small intestinal submucosa (SIS) hydrogel to form a good peri-implant seal. The results show that hydrogel can improve the biological barrier function around implants by combining antibacterial, promoting soft tissue healing and promoting epithelial bonding. This means that the morphology and anti-infection ability of soft tissue are enhanced, which ensures the long-term stability of the implant.SIS-Hst1 hydrogel has certain clinical application in the prevention and early treatment of peri-implantitis. In conclusion, Hst1-SIS hydrogel, as a local administration system, provides experimental evidence for the prevention of peri-implant disease.