HighlightsPeriplaneta americanaL. derived exosome-like nanoparticles (PA-ELNs) as a novel wound healing accelerator was isolated and proved.Protein and small RNA components in PA-ELNs were characterized by omics technology.PA-ELNs remarkably accelerated diabetic wound healing, and were involved in anti-inflammatory, re-epithelialization and autophagy regulation in this process.