CYBB and periodontitis: <i>In vivo</i>, pharmacological inhibition of NOX2 attenuated ferroptosis, mitigated alveolar bone loss, and ameliorated periodontal pathology in mice.<h4>Conclusions</h4>NOX2 activation promoted periodontitis by driving ferroptosis via the ROS/JAK2-STAT3 pathway, highlighting its potential as a novel therapeutic target.