Peptide coupling reagents are vital in peptide synthesis, which is required for the creation of proteins and the research of their structure and function. These chemicals aid in the formation of peptide bonds by connecting amino acids, allowing for the formation of longer peptide chains or proteins. The carboxyl group of one amino acid is linked to the amino group of another, resulting in the formation of a peptide bond. Dicyclohexylcarbodiimide (DCC) is a common peptide coupling reagent. DCC activates an amino acid's carboxyl group by producing an active intermediate known as an O-acylisourea, which combines with the amino group of another amino acid. However, DCC has limits due to its proclivity to produce N-acylurea byproducts, which can obstruct the establishment of the required peptide bond and necessitate additional purification processes. Alternative coupling reagents have been developed to overcome these issues.When compared to DCC, N,N'-diisopropylcarbodiimide (DIC) is one such reagent that reduces the generation of N-acylurea byproducts.DIC efficiently activates carboxyl groups and facilitates peptide bond formation. Furthermore, DIC is soluble in a variety of organic solvents, boosting its adaptability in a variety of peptide synthesis circumstances. N-Hydroxybenzotriazole (HOBt) is another prominent reagent that is used in conjunction with DIC or DCC.HOBt enhances peptide coupling reaction efficiency by increasing the stability of the reactive intermediate and inhibiting side reactions. It serves as a catalyst, minimizing the creation of unwanted byproducts while improving the yield of the intended peptide bond. OxymaPure® is a relatively new peptide coupling reagent. It promotes high-quality peptide synthesis by increasing efficiency and decreasing racemization. OxymaPure® works by increasing carboxyl group activation while decreasing impurity production, hence speeding up the peptide synthesis process. Furthermore, coupling reagents like EDC (1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide) and HATU (O-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate) have gained popularity for their efficacy in amide bond formation and reduced formation of byproducts, contributing to cleaner reactions and improved yields. In conclusion, peptide coupling reagents are essential in peptide synthesis because they allow for the controlled and efficient creation of peptide bonds. Their developments in peptide synthesis continue to focus on improving reaction efficiency, eliminating byproducts, and simplifying purification processes, fostering advancements in a variety of disciplines such as medicine, biotechnology, and biochemical research.