Display omitted •l-histidine and l-carnosine inhibited d-galactose-induced skin aging.•l-histidine and l-carnosine improved skin proliferation and migration in d-galactose-induced skin aging models.•l-histidine and l-carnosine improved collagen and wound healing in d-galactose-induced skin aging.•l-histidine and l-carnosine regulated the levels of corticosterone and PI3K/Akt phosphorylation in skin wound. Impaired skin wound healing in the elderly can lead to medical issues and increased mortality. Although l-histidine and l-carnosine are potent anti-aging amino acids, the wound healing effects of these amino acids in aging remain to be elucidated. Here, we investigated the regenerative potential of l-histidine and l-carnosine in in vitro and in vivo aging models. l-histidine (1 mM), l-carnosine (10 mM), or a combination improved proliferation, migration, senescence, and epithelial-mesenchymal transition (EMT) in d-galactose-induced aged keratinocytes. An in vivo mouse aging model was established with injection of d-galactose (s.c. 500 mg/kg) daily for eight weeks. Supplementation with l-histidine (2 g/L), l-carnosine (2 g/L), or a combination improved collagen and wound healing with EMT markers, E-cadherin, N-cadherin, and MMP-2. These effects were concomitant with reduced circulating levels of corticosterone and increased PI3K/Akt phosphorylation. These results suggest that l-histidine and l-carnosine have the potential to facilitate wound healing in aging skin.