Delayed wound healing in diabetes is aggravated by chronic inflammation and impaired keratinocyte migration. Although zinc facilitates skin wound healing, its excessive accumulation may induce cytotoxicity. This study explores the synergistic potential of zinc and the GPR39 agonist TC-G-1008 in enhancing diabetic wound repair. In vitro , cotreatment reduced lipopolysaccharide-induced pro-inflammatory cytokine expression and promoted keratinocyte migration. In vivo , a hydrogel incorporating zinc oxide nanoparticles and TC-G-1008 accelerated wound closure in diabetic mice and suppressed interleukin-1β expression. Notably, TC-G-1008 alone enhanced keratinocyte migration under diabetic conditions, highlighting its critical role in modulating inflammation. These findings support a zincsparing therapeutic approach using GPR39 activation to restore wound healing in diabetic settings.