Honey has been considered as a remedy in wound healing since ancient times. However, as yet, there are inadequate supportive robust randomized trials and experimental data to fully accept honey as an effective medical product in wound care. Manuka honey has been claimed to have therapeutic advantages over other honeys. Recently, it has been documented that the pronounced antibacterial activity of manuka honey is due, at least in part, to reactive methylglyoxal (MG). The concentration of MG in manuka honeys is up to 100-fold higher than in conventional honeys. MG is a potent protein-glycating agent and an important precursor of advanced glycation end products (AGEs). MG and AGEs play a role in the pathogenesis of impaired diabetic wound healing and can modify the structure and function of target molecules. This commentary describes the concern that MG in manuka honey may delay wound healing in diabetic patients. Further detailed research is needed to fully elucidate the participation of honey/derived MG in healing diabetic ulcers. We advocate randomized controlled trials to determine efficacy and safety of manuka honey in this population.