Long and automatic control of blood glucose levels in diabetic patients could solve the problems caused by frequent insulin injections. Herein, we exploited the protection potential of erythrocytes by a "hitchhiking" strategy to significantly prolong the blood circulation time of a specifically-designed smart hitchhiking insulin delivery system (SHIDS). In the SHIDS, insulin, glucose oxidase, and catalase were co-loaded into nanoparticles formed by modified chitosan. The free glucosamines in chitosan anchor glucose transporters on the surface of erythrocytes, allowing erythrocyte-hitchhiking in the blood flow. A high glucose level triggers quick insulin release from the SHIDS to reduce the glucose level, which then slows the insulin release. This closed-loop glucose regulation by the SHIDS effectively controlled blood glucose within the normal range for at least 24 h and under 250 mg dL-1 for ∼48 h with one injection. This injectable erythrocyte-hitchhiking nanoplatform, which achieves long-term and automatic blood glucose control, thus has potential for further development. As the carrier could be used for delivering other drugs/agents or interacting with other substances, the hitchhiking strategy is versatile and may be applied in other medical applications too.