Disulfide bonds contribute to the stabilization of the three-dimensional structure of proteins and peptides, and play an important role in the expression of their biological activities. However, disulfide bonds are easily cleaved by reducing agents and enzymes, which may result in decreased activity. To prevent this limitation, there are several methods of replacing the disulfide bonds in the peptide chain with other stable bonds. Ring-closing metathesis (RCM) is one such method and is used to synthesize peptides in which disulfide bonds are replaced with carbon-carbon double bonds. Although there are many reports of RCM of protected peptides on solid support, there is a drawback that it is difficult to monitor the reaction progress. In addition, since RCM of protected peptides is generally performed in organic solvents, there are concerns about the solubility of long-chain peptides. On the other hand, since unprotected peptides are generally more soluble in water, RCM of unprotected peptides in water could be an effective method for synthesizing dicarba-peptides. In this presentation, we report that RCM of unprotected peptides in water can be achieved using water-soluble Ru catalyst.