Dedicator of cytokinesis 2 (DOCK2) is a key molecule for lymphocyte activation and migration. DOCK2 interacts with Ras-related C3 botulinus toxin substrate 1 (Rac1, GTPase) and mediates the GDP-GTP exchange reaction, indicating that inhibitors against protein-protein interaction (PPI) between DOCK2 and Rac1 would be good drug candidates for treating immune-related disorders. Here, we report DOCK2selective PPI inhibitory peptides discovered using random peptide T7 phage display technology. These peptides inhibited DOCK2 activity at nanomolar concentrations and were delivered to intracellular compartments by combination with cell-penetrating peptide (CPP). Consequently, one peptide, R4-DCpep-2(V2W/ K4R/ ox)-NH2 (Ac-RRRRCWARYHGYPWCRRRR-NH2), inhibited migration in human B lymphocyte MINO cell line at IC50 = 120 nM. To our knowledge, this is the first report of a DOCK2-selective peptide inhibitor; this study will contribute to the development of novel DOCK2-targeting immunosuppressive drugs. (C) 2016 Elsevier Inc. All rights reserved.