Lung cancer is one of the most diagnosed type of cancers in the world. The treatment of non-small cell lung cancer (NSCLC) still remains a challenge despite advances in chemotherapy and other methods of treatment in the last decade. The goal of this study was to prepare and evaluate a PLGA-chitosan based nanoparticle delivery system to passively target the delivery of meclinertant to NSCLC cell line. Poly-lactic glycolic acid (PLGA) nanoparticles were synthesized using single emulsification and evaporation method. The characterization and physicochemical evaluation were performed using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Zeta potential, particle size analysis, and in-vitro drug release. Cytotoxicity analysis revealed that meclinertant-loaded-chitosan-coated PLGA nanoparticles had significantly higher antiproliferative effect on A549 cells as compared to meclinertant alone in A549 cells. Coating with chitosan had a significant increase in the uptake of nanoparticles in A549 cells. The nuclear apoptotic activity using Hoechstt 33342/Propidium iodide (PI) dual staining suggests that meclinertant is able to induce apoptosis in A549 cells. In conclusion, meclinertant-loaded-chitosan-coated PLGA nanoparticles shows promise as a potential treatment option for NSCLC.