The blood brain barrier (BBB) is a formidable impediment in the treatments of glioma. Despite a variety of drug carriers have been developed to help drug penetrate BBB, biological security is still a major concerns. In this study, we designed DNA tetrahedron nanostructures for brain-targeting drug delivery, which has excellent biological compatibility. Angiopep-2, a brain-targeting peptide was used to modify DNA tetrahedron to help for penetrating through the BBB. The results show that Angiopep-2 modified DNA tetrahedron has good stability in serum and excellent biocompatibility.