Triple-negative breast cancer is one of the most prevalent malignant cancers worldwide. Disrupting the MTDH-SND1 protein-protein interaction has recently been shown to be a promising strategy for breast cancer therapy. In this work, a novel potent stabilized peptide with a stronger binding affinity was obtained through rational structure-based optimization. Furthermore, a sulfonium-based peptide delivery system was established to improve the cell penetration and antitumor effects of stabilized peptides in metastatic breast cancer. Our study further broadens the in vivo applications of the stabilized peptides for blocking MTDH-SND1 interaction and provides promising opportunities for breast cancer therapy.