Microneedle technology is valuable in wound treatment. Current studies focus on optimizing the function of microneedles and screening for effective encapsulated actives. Herein, we develop innovative MXene hydrogel microneedles with nitric oxide (NO) and hypoxia-inducible factor-1α (HIF-1α) plasmid controllable release for diabetic wound treatment. These microneedles consist of gelatin coupled with tert-butyl nitrite (Gel-SNO) polymers obtained by conjugating the –SNO group on the gelatin side chain, therefore, NO can be generated and released under near-infrared (NIR) light irradiation owing to the thermal effect. Simultaneously, by harnessing the enhanced photothermal conversion efficiency of the MXene additive, the microneedle patch can quickly dissolve and liberate the enclosed HIF-1α plasmid nanoparticles into the dermis when exposed to NIR radiation. The released NO effectively reduced the inflammatory response and released HIF-1α plasmid induced neovascularization. Thus, in vivo experiments showed that these microneedles could accelerate wound closure by alleviating inflammation, and promoting re-epithelialization and angiogenesis. These results indicated the potential value of MXene hydrogel microneedles in wound healing and other related biomedical fields.