Background <p>Oxidative stress plays a significant role in the progression of periodontal diseases. Hexagonal boron nitride (hBN) nanoparticles have antimicrobial, antiplaque, and antioxidant properties. The aim of this study to evaluate the protective and therapeutic effects of hBN against oxidative stress induced by hydrogen peroxide (H₂O₂) in human gingival fibroblast (HGF) cells.</p> Methods <p>In this study, a primary cell line of HGFs was used. Oxidative stress was induced by treating the cells with 800 µM H₂O₂. hBN was applied at concentrations of 0.001, 0.005, and 0.01&#xa0;mg/mL, either 2&#xa0;h prior to or 2&#xa0;h following H₂O₂ exposure. Cells were incubated for 24&#xa0;h post-treatment. Cell viability was assessed using the 2,3-bis-[2-methoxy-4-nitro-5-sulfophenyl]-2&#xa0;H-tetrazolium-5-carboxyanilide salt (XTT) assay. Additionally, the total oxidant status (TOS) was measured before and after oxidative damage at the 0.01&#xa0;mg/mL hBN concentration.</p> Results <p>hBN did not negatively affect cell viability in HGF cells at any concentration. The application of hBN to HGF cells before and after oxidative damage resulted in statistically significant (<i>P</i> &lt; 0.001), albeit modest improvements in cell viability (2-5.5% and 3-6.5%, respectively). No significant differences were observed in TOS (<i>P</i> = 0.234), indicating that the cytoprotective effects were not mediated via alterations in TOS.</p> Conclusions <p>Within the limitations of this in vitro study, hBN was found to enhance cell viability under H₂O₂-induced oxidative stress in HGF cells. These findings suggest a potential role for hBN in modulating antioxidant responses and supporting periodontal healing processes. However, their clinical relevance remains uncertain. Therefore, further mechanistic studies and clinical investigations are required to validate the potential adjunctive role of hBN in the prevention and treatment of periodontal diseases.</p>