The aims of this study were to develop and characterize curcumin (CCM) and docetaxel (DTX) co-loaded poly lactide-co-glycolide (PLGA) nanoparticles (NPs) to overcome blood brain barrier. The cytotoxicity of the obtained curcumin and docetaxel co-loaded polysorbate 80 coated PLGA NPs were studied in U87 glioma cells and bEND.3 endothelial cells. The IC50 values are determined for both cell lines. In vitro release profile of the optimized formulation approximately 27% of DTX was released in the 1. hour and after a steady controlled release the DTX released percentages plateaued after 48. hour. In vitro curcumin release profile had a more controlled released by releasing less than 8% in the 1. hour and plateaued after 48. hour at approximately 78% curcumin released. Polysorbate 80 coated DTX-CCM-PLGA NPs showed no cytotoxicity and had better uptake in bEND.3 cells than uncoated DTX-CCM- PLGA NPs. The combination of CCM and DTX in PLGA nanoparticles showed a significant increased cytotoxic activity compared to CCM and DTX solutions, CCM loaded PLGA NPs and DTX loaded PLGA NPs. Moreover, in vivo biodistribution studies show that polysorbate 80 coating significantly improve brain penetration. Polysorbate 80 coated CCM and DTX loaded PLGA Nanoparticles can be potentially useful in the treatment of glioma by increasing the delivered quantity of drug in the brain through blood-brain barrier.