The ascendant danger of bacterial infections has resulted in an urgent requirement for developing new antibacterial approaches. Recently, nitric oxide (NO) has shown a broad-spectrum antimicrobial activity while avoiding resistance. However, achieving effective NO-based antibacterial therapies remains challenging, mired by the safety concerns of NO donor, residual toxicity by the ingredients, or complicated procedures. Herein, a self-activated NO-releasing hydrogel depot is fabricated by Ca²⁺-crosslinked sodium alginate doped with CaO₂ nanoparticles, L-arginine, and oxidized mesoporous carbon nanoparticles (OMCN) for photothermal enhanced bacteria killing. The locally concentrated H₂O₂, generated from the reaction of CaO₂ nanoparticles and water, could oxidize L-arginine to release NO. Meanwhile, benefiting from the remarkable photothermal effect of OMCN, the hybrid hydrogel possesses a synergistic sterilization behavior in combating both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria in vitro. Moreover, the dual therapeutic hydrogel displays high efficiency in treatment of bacteria-infected mice with back wound model while showing no distinct toxicity. In addition, the restricted environment of hydrogel makes it easy to remove all the components from the infected wound, alleviating possible side effects from exogenous H₂O₂. As such, the designed NO-synergistic photothermal hydrogel provides a promising strategy for treating bacterial infections.