The purpose of this study was to examine low molecular weight chitosan-grafted polylactide nanoparticles as a drug delivery system for doxorubicin and temozolomide. We investigated the effect of polylactide molecular weight on the release kinetic and encapsulation efficiency of both drugs. Polylactide (10 kDa and 60 kDa) has been linked to chitosan via coupling reaction. Chitosan-grafted-polylactide nanoparticles were prepared via ionotropic gelation method with tripolyphosphate as a linking agent. Results such as size (150-350 nm), -potential (+25-35 mV), efficient encapsulation and prolonged release kinetic suggested that chitosan-grafted-poly lactic acid could be a great system for co-delivery of doxorubicin and temozolomide in Glioblastoma Multiforme treatment.