Amino acids are significant for human life and therefore considered as the crucial nutrients for human body with high biosafety. Due to their high biocompatibilities and various physicochemical properties, their polymers can be applied to construct drug delivery systems for various diseases' treatments. Among them, glioblastoma multiforme received special attention and numerous efforts regarding to nanotechnology were developed to treat such tumor. However, the biosafety of the delivering materials in those efforts arises as a critical issue in consideration of the weak patients. Therefore, a ROSresponsive nanoparticle (DOX@PLSPL) with poly(amino acids) encapsulating doxorubicin was developed for glioblastoma multiforme treatment. DOX@PLSPL was constructed by poly-lysine and poly-leucine with high biocompatibility. The high doxorubicin encapsulation efficiency and the controlled release manner of DOX@PLSPL ensured its high anti-tumor effect. Totally, this DOX@PLSPL can be used as a promising drug delivery system for glioblastoma multiforme treatments.