Chronic wound healing remains a considerable clinical challenge worldwide. We previously identified a pro-regenerative agent, i.e., hollow dopamine nanoparticles (HPDA) loaded with potent pro-healing pep-tide RL-QN15 (HPDAlR), with significant skin wound healing activity. In the current study, in considera-tion of clinical application, we successfully prepared a new zinc alginate hydrogel embedded with HPDAlR (HPDAlR&ZA) to treat diabetic wounds. HPDAlR&ZA exhibited no obvious toxicity against ker-atinocytes, human umbilical vein endothelial cells (HUVECs), human skin fibroblasts (HSFs), and mice. HPDAlR&ZA significantly promoted keratinocyte, HUVEC, and HSF proliferation, as well as HUVEC migra-tion and angiogenesis. HPDAlR&ZA also modulated the expression of cytokines from macrophages. Diabetic mouse full-thickness skin wound and diabetic patient in vitro skin wound models showed that HPDAlR&ZA resisted the inflammatory response by rapidly polarizing M1 macrophages to M2 macro-phages, thereby reconstructing blood supply, increasing collagen deposition, and accelerating diabetic wound repair and skin regeneration. In summary, HPDAlR&ZA is a biodegradable hydrogel wound dress-ing and an efficient treatment strategy for diabetic wound repair, with strong anti-oxidant, anti-inflammatory, and pro-angiogenic features. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).