Identification of cysteines with high oxidation susceptibility is important for understanding redox-mediated biological processes. In this report, we report a chemical proteomic strategy that finds cysteines with high susceptibility to S-glutathionylation. Our proteomic strategy, named clickable glutathione-based isotope-coded affinity tag (G-ICAT), identified 1,518 glutathionylated cysteines while determining their relative levels of glutathionylated and reduced forms upon adding hydrogen peroxide. Among identified cysteines, we demonstrated that CTNND1 (p120) C692 has high susceptibility to glutathionylation. Also, p120 wild type (WT), compared to C692S, induces its dissociation from E-cadherin under oxidative stress, such as glucose depletion. p120 and E-cadherin dissociation correlated with E-cadherin destabilization via its proteasomal degradation. Lastly, we showed that p120 WT, compared to C692S, increases migration and invasion of MCF7 cells under glucose depletion, supporting a model that p120 C692 glutathionylation increases cell migration and invasion by destabilization of E-cadherin, a core player in cell-cell adhesion. Display omitted •Chemical proteomics identifies cysteines highly susceptible to glutathionylation•p120 C692 is highly susceptible to glutathionylation•p120 C692 glutathionylation induces degradation of E-cadherin•p120 C692 glutathionylation contributes to migration of epithelial cells Kukulage et al. developed a chemical proteomic strategy that identifies functional cysteines highly susceptible to glutathionylation, including C692 of p120 catenin, and found that p120 C692 glutathionylation serves as a regulatory mechanism of cell-cell adhesion under cellular stress.