Peptides are a promising source of new therapeutics, but the biophysical characteristics of natural peptides, including their stability and propensity to aggregate, can limit their success. Protein engineering offers powerful tools to improve the properties of peptides for biological applications. In this review, we explain rational design, directed evolution, and computational methods and how these methods can be applied to improving the characteristics of peptides. We also provide a discussion of engineering the thermodynamic stability, self‐assembly, reduced aggregation, proteolytic stability, and binding affinity and specificity of peptides, along with a perspective on future directions in engineering therapeutic peptides.

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