OBJECTIVE: To investigate the protective role of F-box/WD repeat domain-containing 7 in rat periodontal ligament stem cells under oxidative stress. MATERIALS AND METHODS: The apoptosis of rat periodontal ligament stem cells was induced by exposure to various concentrations of hydrogen peroxide for 24 h, after which cell viability and the cleaved caspase-3 and -9 levels were determined. The levels of proteins in the Notch signaling pathway were determined by western blotting. RESULTS: The overexpression of F-box/WD repeat domain-containing 7 increased cell viability following hydrogen peroxide administration and suppressed the activation of caspases-3 and -9. The overexpression of F-box/WD repeat domain-containing 7 inhibited Notch signaling. Furthermore, the protective effect of F-box/WD repeat domain-containing 7 could be resumed by PF-03084014, a Notch-specific inhibitor. CONCLUSIONS: These observations suggest a protective role of F-box/WD repeat domain-containing 7 against hydrogen peroxide-induced oxidative stress in rat periodontal ligament stem cells. These findings will facilitate the in vitro culturing of periodontal ligament stem cell for clinical usage and promote stem cell-based therapy for periodontal tissue regeneration.