Vanadium compounds are promising anti-diabetic agents, and graphene quantum dots (GQDs) are emerging as potential drug delivery systems to improve drug solubility in water and membrane transport. Using highly dispersible and water-soluble GQDs, we herein prepared a novel GQD-VO (p-dmada) complex, in which vanadium coordination compounds [VO(p-dmada)] were packed closely on one side of the GQD sheets possibly via the π-π stacking mechanism. The in vitro tests showed that GQD-VO(p-dmada) exhibited membrane permeability (Papp) as good as that of GQDs with reduced cytotoxicity. In vivo tests on type 2 diabetic mice demonstrated that GQD-VO(p-dmada) exhibited a delayed glucose lowering profile but more profound effects on insulin enhancement and β-cell protection after three-week treatment compared to VO(p-dmada) alone. In addition, GQD alone was observed for the first time to effectively lower the blood lipid levels of the db/db mice. Overall, GQD-VO(p-dmada) showed improved pharmacokinetic performance and hypoglycemic effects, and using GQD as a nanoplatform for drug delivery may provide vast opportunities for the further design of metal-based pharmaceutical agents.