Objectives <p>Atrial fibrillation (AF), the most prevalent type of cardiac arrhythmia, is associated with high morbidity and mortality. The pharmacological management of AF is still challenging due to the risk of life-threatening ventricular arrhythmias caused by non-selective antiarrhythmic drugs. Therefore, the search for safer and more selective anti-AF medications is ongoing. In this study, we summarized phytochemicals with atrial-selective properties as potential candidates for AF drug discovery.</p> Evidence acquisition <p>PubMed, Embase, Web of Science, and Scopus were searched using relevant keywords, ultimately identifying sixteen phytochemicals with demonstrated effects on atrial-selective anti-AF targets.</p> Results <p>Across the included studies, phytochemicals were reported to modulate several atrial-selective ion channels, including voltage-gated K⁺ channel 1.5, voltage-gated Na⁺ channel 1.5, and G-protein-activated, inward rectifying K⁺ channel 1 and 4, with some compounds affecting more than one target. The most investigated phytochemicals were acacetin, resveratrol, and its derivative C1, and eleutheroside B, all of which demonstrated anti-AF effects in association with their activity on atrial-selective pathways. Acacetin and resveratrol derivatives exerted anti-AF effects through modulation of multiple atrial-selective ion channels.</p> Conclusion <p>The findings of this study highlight several promising molecular targets for atrial-selective anti-AF drug development. Among these, acacetin and resveratrol derivatives show notable potential due to their ability to modulate multiple atrial-selective ion channels, supporting their further evaluation as lead compounds.</p> Graphical Abstract <p></p>