In recent years, the incidence of diabetic skin ulcers has increased. Because of its extremely high disability and fatality rate, it brings a huge burden to patients and society. Platelet-rich plasma (PRP) contains a large number of biologically active substances and is of great clinical value in the treatment of various wounds. However, its weak mechanical properties and the consequent abrupt release of active substances greatly limit its clinical application and therapeutic efficacy. Here, we chose hyaluronic acid (HA) and ε-polylysine (ε-PLL) to prepare a hydrogel with the ability to prevent wound infection and promote tissue regeneration. At the same time, using the macropore barrier effect of the lyophilized hydrogel scaffold, platelets in PRP are activated with calcium gluconate in the macropores of the scaffold carrier, and fibrinogen from PRP is converted in a fibrin-packed network forming a gel that interpenetrates the hydrogel scaffold carrier, thus creating a double network hydrogel with slow-release of growth factors from degranulated platelets. The hydrogel not only showed better performance in functional assays in vitro, but also showed more superior therapeutic effects in reducing inflammatory response, promoting collagen deposition, facilitating re-epithelialization and angiogenesis in the treatment of full skin defects in diabetic rats.