Genetic code reprogramming is the method to redesign the genetic code restricted by 20 proteinogenic amino acids with other exotic building blocks. Although there are some ways to reprogram the genetic code, flexizymes invented by Suga and colleagues are highly versatile catalysts to charge a wide range of such amino acids, including D-amino acids, beta/gamma-amino acids, and hydroxy acids. The combination of flexizyme technology with a custom-made cell-free translation system, referred to as Flexible In-vitro Translation (FIT) system, enables for expression of libraries of nonstandard peptides containing exotic building blocks. This method is further integrated with mRNA display has led to the invention of RaPID (Random nonstandard Peptides Integrated Discovery) system, giving ultrafast discovery of de novo bioactive peptides. This lecture will discuss the discovery history of flexizymes and applications of the genetic code reprogramming to peptide therapeutic innovation.