In this study, we evaluate the feasibility of targeting CtBP‐overexpressing tumors through a therapeutic peptide capable of disrupting the CtBP transcription factor complex, using the H1299 non‐small cell lung cancer cells and the A375 melanoma cells for in vitro experiments and a xenograft mouse melanoma model for in vivo experiments. The gene discussed is CTBP1; the disease is melanoma.