Oxidative stress mediated by NADPH oxidase 2 (NOX2), a major source of reactive oxygen species in the myocardium, is an important mechanism that underlies cardiac arrhythmias. NOX2 is activated by the precise assembly of multiple protein subunits. It plays a critical role in initiating and sustaining atrial fibrillation and ventricular arrhythmias by disrupting calcium homeostasis, differentially regulating ion channel function, and inducing structural remodeling. Notably, a close association between NOX2 and arrhythmias is well-established, and interventions targeting NOX2 have demonstrated therapeutic potential. However, the signaling pathways through which NOX2 modulates myocardial electrophysiology under different pathological states remain unclear. Moreover, the dynamic coupling of NOX2 with upstream risk factors, such as abnormal cardiac load and metabolic diseases, remains poorly characterized. In this review, we summarize the structure, activation mechanisms, arrhythmogenic mechanisms, and targeted strategies of NOX2, providing a comprehensive reference for understanding its role in cardiac electrical remodeling and developing antiarrhythmic therapies.