Triple-negative breast cancer is an aggressive cancer with high metastatic potential and limited treatment options. The current study investigated the anticancer activity of the Polybia-derived MP-1 peptide, formulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles, for inhibiting PD-L1 and epithelial mesenchymal transition (EMT)-associated signalling in triple-negative breast cancer (TNBC). Computational screening of molecules identified MP-1 as a stable high-affinity binder of PD-L1 possessing high anticancer prediction scores. The MP-1-PLGA nanoparticles that were optimized showed the spherical structures with a size of 104.4 nm as well as a PDI of 0.231. Moreover, their encapsulation efficiency was 71.5%. The formulation showed a controlled release with 41.65% over 72 h (p