The study investigates therapeutic potential of PLGA-NDP in OECM-1 oral cancer cells. PLGA-NDP presented higher cytotoxicity, lower redox reaction, and higher release activity in relation to nedaplatin alone. With PLGA-NDP treatment the colony formation assay exhibited a substantial minimize in cell survival. PLGA-NDP also moderate MMP-9 release, indicating inhibition of cellular degranulation. The dose-dependent responses and increased efficacy in relation to nedaplatin alone recommend the potential of PLGA-NDP as novel therapy for oral cancer. These results advise that PLGA-NDP nanoparticles may be more efficient alternative to conventional nedaplatin therapy in cancer treatment, which may result in higher efficiency and decline adverse effects.