Small molecules are only able to target the small population of human proteins containing a hydrophobic pocket which is a major problem in traditional small molecule drug development. Peptide based therapeutics offer the potential to target a much wider range of targets by inhibiting protein-protein interactions. The major drawbacks of peptide therapeutics include lack proteolytic stability and ill-defined secondary structures. These problems can be eloquently overcome by incorporation of unnatural amino acids into potential therapeutics to lower the rate of proteolytic cleavage and by creating cyclic peptides to lock the peptide into a conformation which lowers the entropic penalty of binding. Indeed, there are numerous examples of unnatural peptides exhibiting enhanced pharmacokinetics over their parent peptides. Taking in all these considerations, the ability to create libraries of random peptides containing unnatural amino acids is an appealing endeavor. Through a reconstituted cell-free translation system we demonstrate how an editing deficient valine tRNA synthetase (ValRS T222P) can be used for the incorporation of 13 unnatural amino acids into peptides including three cyclic beta amino acids and three alpha methyl amino acids. This system has the potential to be applied to the ligand discovery tool of mRNA display for identification of potent peptide inhibitors of disease relevant protein-protein interactions.