DPMI-ω is a dual-specific D-peptide antagonist of the carcinogenic proteins MDM2 and MDMX. When loaded onto gold nanoparticles, DPMI-ω effectively penetrates tumor cells and kills them by reactivating the p53 signaling pathway. It disrupts the p53-MDM2/MDMX complex and inhibits the growth of B16 melanoma while inducing G0/G1 phase cell cycle arrest. Combined with anti-PD1 antibodies, DPMI-ω enhances immunotherapy by amplifying CD3+/CD8+ cytotoxic T cells and inhibiting CD4+/CD25+ regulatory T cells. DPMI-ω is applicable in melanoma research.