Precise targeted delivery of therapeutic agents is crucial for tumor therapy. As an emerging fashion, cell-based delivery provides better biocompatibility and lower immunogenicity and enables a more precise accumulation of drugs in tumor cells. In this study, a novel engineering platelet was constructed through cell membrane fusion with a synthesized glycolipid molecule, DSPE-PEG-Glucose (DPG). The obtained glucose-decorated platelets (DPG-PLs) maintained their resting state with structural and functional integrities, while they would be activated and triggered to release their payloads once they arrive at the tumor microenvironment. Glucose decoration was verified to impart the DPG-PLs with stronger binding effects toward tumor cells that overexpress GLUT1 on their surfaces. Together with the natural homing property toward tumor sites and bleeding injury, doxorubicin (DOX)-loaded platelets (DPG-PL@DOX) exhibited the strongest antitumor effects on a mouse melanoma model, and the antitumor effect was significantly enhanced in the tumor bleeding model. DPG-PL@DOX provides an active and precise solution for tumor-targeted drug delivery, especially for postoperative treatments.