Protein-protein interactions (PPIs) play a central and crucial role in almost every cellular process. Understanding the structural basis of protein-protein interactions can lead to the development of new drugs for treatment of various diseases. With this purpose, peptide-based drug design (PBDD) has been extensively explored in the last few decades. Peptidomimetics are compounds which mimic the biological activity of peptides while offering the advantages of improving their pharmacokinetics profiles. In this review, we would like to summarize the state of the art of computational methods which have been recently introduced to design novel peptidomimetics involved in a therapeutically relevant protein-protein recognition processes.