In the stratum corneum, the intercellular junction made up of cadherin proteins provides the structural integrity of the framework. Ca2+ ions are known to play a key role in maintaining this junction. In this study, we hypothesized that Ca2+ chelation in stratum corneum will weaken the bond of the tissue and consequently promote exfoliation. Amino acids, ubiquitously existing as metabolites and building blocks of the body, have the molecular property to chelate Ca2+ ions. In the current study, we verified the Ca2+ chelating property of amino acids and demonstrated that amino acids can interfere with the interaction of cadherins, separate stratum corneum into pieces, and thereby stimulate the exfoliation process of skin. These results validate the importance of Ca2+ ion in the skin exfoliation process. Importantly, our findings indicate that amino acids may be efficiently used for improving skin conditions.