Graphene-2D carbon-has received significant attention thanks to its electronic, thermal, and mechanical properties. Recently, nano-graphene (nGr) has been investigated as a possible platform for biomedical applications. Here, a polymer-coated nGr to deliver drugs to glioblastoma after systemic administration is reported. A biodegradable, biocompatible poly(lactide) (PLA) coating enables encapsulation and controlled release of the hydrophobic anticancer drug paclitaxel (PTX), and a hydrophilic poly(ethylene glycol) (PEG) shell increases the solubility of the nGr drug delivery system. Importantly, the polymer coating mediates the interaction of nGr with U-138 glioblastoma cells and decreases cytotoxicity compared with pristine untreated nGr. PLA-PEG-coated nGr is also able to encapsulate PTX at 4.15 wt% and sustains prolonged PTX release for at least 19 d. PTX-loaded nGr-PLA-PEGs are shown to kill up to 20% of U-138 glioblastoma cells in vitro. Furthermore, nGr-PLA-PEG and CNT-PLA-PEG, two carbon nanomaterials with different shapes, are able to kill U-138 in vitro as well as free PTX at significantly lower doses of drug. Finally, in vivo biodistribution of nGr-PLA-PEG shows accumulation of nGr in intracranial U-138 glioblastoma xenografts and organs of the reticuloendothelial system.