Harnessing cross-species regenerative cues to direct human regenerative potential is increasingly recognized as an excellent strategy in regenerative medicine, particularly for addressing the challenges of impaired wound healing in aging populations. The skin mucus of Andrias davidianus plays a critical role in self-protection and tissue repair, yet the fundamental regenerative factors and mechanisms involved remain elusive. Here, this work presents evidence that glycosaminoglycans (GAGs) derived from the skin secretion of Andrias davidianus (SAGs) serve as potent mediators of angiogenesis and inflammatory remodeling, facilitating efficient healing of diabetic wounds. Mechanistic studies reveal that SAGs promote macrophage polarization toward an anti-inflammatory and pro-regenerative phenotype (CD206