Managing open skin wounds remains a notable challenge in clinical practice, with wound dressings gradually becoming an essential strategy for such treatment. To effectively regulate the wound healing microenvironment, we developed an antibiotic-free nanocomposite hydrogel by combining guanosine-based supramolecular G-quadruplexes (G4), angiogenic deferoxamine (DFO), konjac glucomannan (KGM), and zinc ions through a one-pot mixing strategy. The borate esters in G4 endow the hydrogel with a strong radical-scavenging ability. As a mannose-containing polysaccharide, KGM does not affect the self-assembly of G-quartets and also induces macrophage polarization toward the anti-inflammatory M2 phenotype without requiring expensive exogenous cytokines. Zinc ions were introduced to enhance the hydrogel's mechanical properties by forming coordination interactions with DFO and endowing the hydrogel with excellent antibacterial properties. Collectively, this biocompatible hydrogel accelerates skin wound closure and promotes mature tissue regeneration by stimulating macrophage polarization toward the M2 phenotype, expediting collagen deposition, alleviating inflammation, and enhancing angiogenesis. Overall, this multifunctional hydrogel can serve as a versatile wound dressing material in regenerative medicine.