Sea stars are an abundant group of marine invertebrates that display remarkably robust regenerative capabilities throughout all life stages. Numerous proteins and peptides have been identified in a proteome study on the coelomic fluid (biofluid) of the common sea star Asterias rubens, which appear to be involved with the wound-healing response. However, the three-dimensional structure and function of several of these injury-responsive peptides has yet to be investigated, including the 28-residue peptide KASH2. Here we show this peptide adopts a disulfide-directed β-hairpin fold (DDH). The DDH motif appears to be evolutionarily related to the inhibitor cystine knot motif, which is one of the most widespread disulfide-rich peptide folds. The DDH motif was originally thought to be restricted to arachnids, but our study suggests that it could have originated in sea stars as a result of convergent evolution. The widely conserved DDH fold has potential cross-phyla wound healing capacity, but we showed that KASH2 does not enhance the proliferation of human fibroblasts, a simple method for wound healing re-epithelialisation screening. Therefore, additional research is necessary to determine the role of KASH2 in the sea stars.