Background
With the rising demand for peptide-based drugs, enhancing their stability against proteolytic degradation has become a critical challenge. Strategies to improve peptide stability include cyclization, substitution of L-amino acids with D-amino acids, incorporation of β-amino acids, and various formulation techniques. An innovative approach involves modifying the peptide backbone by reversing the amide bond direction and inverting the stereochemistry of amino acids in the same segment. This approach results in the formation of retro-inverso peptides, which offer increased stability, permeability, and cellular uptake.

Purpose
The aim of this review is to provide a comprehensive analysis of retro-inverso peptides, focusing on their concept, synthesis, and applications as potential therapeutic agents, drug delivery systems, and in aesthetic applications.

Methods
The review explores the theoretical underpinnings of retro-inverso peptide design and its application to both linear and cyclic peptides. The synthesis strategies of retro-inverso peptides are discussed in detail, along with their formulation and practical utility in various biomedical fields.

Results
Retro-inverso peptides show promise in enhancing peptide stability and improving biological properties such as permeability and cellular uptake. Their unique structure offers advantages in drug development and potential as therapeutic agents or drug carriers.

Conclusion
Retro-inverso peptides represent a valuable strategy for overcoming the limitations of conventional peptides, especially regarding stability and bioavailability. This review highlights their potential in therapeutic development and other applications, reinforcing the importance of continued research and innovation in peptide chemistry.