Introduction: Connexin and pannexin (hemi)channels play an important role in paracrine and autocrine signaling pathways. The opening of these cellular pores is linked to a wide range of diseases. Therefore, pharmacological closing of connexin and pannexin (hemi)channels seems a promising therapeutic strategy. However, the currently available inhibitors cope with recurring problems concerning selectivity, specificity, stability and/or solubility. Areas covered: A number of peptides that mimic specific regions in the native sequence of connexins and pannexins have the potential to overcome some of these hurdles. In this paper, an overview is provided on these peptide-based inhibitors of connexin and pannexin (hemi)channels for therapeutic purposes. The authors also provide the reader with their expert perspectives on the future of these peptide-based inhibitors. Expert opinion: Peptide mimetics can become valuable tools in the treatment of connexin-related and pannexin-related diseases. This can be made possible provided that available peptides are optimized, and new peptide mimetics are designed based on knowledge of the mechanisms underlying the gating control of connexin and pannexin (hemi)channels.