The treatment of glioblastoma (GBM) represents an urgent challenge for public health due to the inability to effectively deliver anticancer agents, such as doxorubicin (DOX), through the blood-brain barrier (BBB). Herein we report the synthesis of two novel DOX glycoconjugates using an oxime linkage that maintained the intercalation capability of the planar anthracycline ring of DOX, as demonstrated by UV-vis and fluorescence experiments in the presence of DNA. The biological effect of DOX glycoconjugates was evaluated in GBM cell lines, showing an enhanced cytotoxic and pro-apoptotic effect of as compared to and to conventional DOX. These data were confirmed in an coculture BBB model in which DOX glycoconjugate showed high capability to cross a cellular monolayer and exert its cytotoxic effect on GBM cells. The results show that conjugation with glucose may represent a helpful tool to increase chemotherapy effectiveness in poor-responding GBM patients.