The application of peptide drugs in cancer therapy is impeded by their poor biostability and weak cell permeability. Therefore, it is imperative to find biostable and cell-permeable peptide drugs for cancer treatment. Here, we identified a potent, selective, biostable, and cell-permeable cyclic d-peptide, NKTP-3, that targets NRP1 and KRASG12D using structure-based virtual screening. NKTP-3 exhibited strong biostability and cellular uptake ability. Importantly, it significantly inhibited the growth of A427 cells with the KRASG12D mutation. Moreover, NKTP-3 showed strong antitumor activity against A427 cell-derived xenograft and KRASG12D-driven primary lung cancer models without obvious toxicity. This study demonstrates that the dual NRP1/KRASG12D-targeting cyclic d-peptide NKTP-3 may be used as a potential chemotherapeutic agent for KRASG12D-driven lung cancer treatment.