Current therapies for treating malignant glioma exhibit low therapeutic efficiency because of strong systemic side effects and poor transport across the blood brain barrier (BBB). Herein, we combined targeted chemo-photothermal glioma therapy with a novel multifunctional drug delivery system to overcome these issues. Drug carrier transferrin-conjugated PEGylated nanoscale graphene oxide (TPG) was successfully synthesized and characterized. When loaded on the proposed TPG-based drug delivery (TPGD) system, the anticancer drug doxorubicin could pass through the BBB and improve drug accumulation both in vitro and in vivo. TPGD was found to perform dual functions in chemotherapy and photothermal therapy. Targeted TPGD combination therapy showed higher rates of glioma cell death and prolonged survival of glioma-bearing rats compared with single doxorubicin or PGD therapy. In conclusion, we developed a potential nanoscale drug delivery system for combined therapy of glioma that can effectively decrease side effects and improve therapeutic effects.