<p>In this study, the multifaceted toxicity caused by zinc sulfate (ZnSO₄) and the protective potential of <i>Helichrysum arenarium</i> L. extract against this toxicity were investigated using the model organism <i>Allium cepa</i>. In this context, changes in growth, cytogenetic, biochemical and histological parameters, as well as DNA damage were investigated in groups of <i>A. cepa</i> L. exposed to <i>H. arenarium</i> extract (50 and 100 mg/L<i>)</i>, ZnSO₄ (140&#xa0;mg/L), and their combinations, respectively. The phenolic profile of the extract was also evaluated through LC-MS/MS analysis. ZnSO₄ treatment reduced growth, mitotic index (MI) and chlorophyll pigment levels. Chromosomal aberrations (CAs) and micronucleus (MN) formation as well as lipid peroxidation and antioxidant enzyme (superoxide dismutase and catalase) activities increased following the ZnSO₄ exposure. DNA damage, as measured by the level of DNA fragmentation, also increased significantly in response to ZnSO₄. While both doses of <i>H. arenarium</i> caused no harm when administered alone, when combined with ZnSO₄, the toxic effects were significantly mitigated. In particular, the improvement in growth, the reduction in DNA and membrane damage, the maintenance of chromosomal stability and the recovery of chlorophyll levels suggested a protective effect of the extract. The therapeutic potential of the extract was dose-dependent. Phenolic profile analysis revealed that the extract is rich in phenolic compounds such as apigenin, chlorogenic acid, and luteolin. Given the antioxidant and antigenotoxic potential of these compounds, it is suggested that the extract’s bioprotective effect may be attributable to its phenolic content. This study suggests that <i>H. arenarium</i> extract can exert a multifaceted protective effect against zinc-induced toxicity, thereby offering a new perspective on the use of plant-derived natural compounds against heavy metal stress.</p>