Inadequate oxygenation is one of the chief culprits for delayed wound healing. However, current oxygen therapies, such as hyperbaric oxygen therapy and topical oxygen therapy, face hurdles in providing sustained and long-term oxygenation to reverse wound hypoxia. Furthermore, their efficacy in rejuvenating wound injury is restricted by limited penetration of oxygen in the wound bed. Herein, this study proposes a programmable and portable oxygenation device (named GUFO oxydevice) by ingeniously integrating i) a controllable oxygen generation and unidirectional transmission system (COGT-UTS), and ii) a supramolecular assembled perfluorinated hyperbranched polymer/gelatin (GUF) hydrogel in which the perfluorinated hyperbranched polymer (FHBP) acts as an oxygen reservoir to ensure sustained and convenient oxygen replenishment and thus directly regulate the hypoxic wound microenvironment. Accelerating the wound healing process by GUFO oxydeviceis achieved in both a diabetic rat and an acute porcine wound model without any secondary tissue damages. The present study demonstrates that the GUFO oxydevice holds promise as a practically feasible candidate for wound treatment.