Background <p>Alzheimer's disease (AD), marked by amyloid β peptide buildup leading to neurodegeneration and cognitive decline, is a growing health concern. This study explores the neuroprotective potential of <i>Mimosa pudica</i>, a plant with traditional medicinal uses, focusing on its antioxidant properties and effects in a zinc-induced zebrafish model of AD.</p> Methods <p>AD-like symptoms were induced in zebrafish using zinc oxide nanoparticles (ZnO NPs). The hydromethanolic extract of <i>M. pudica</i> (HMEMP) was analyzed for antioxidant activity through DPPH assays, functional group identification via FTIR, and immunohistochemical staining to observe brain astroglial cells. Behavioral tests were conducted to assess cognitive and social impairments, including open field, mirror biting, light–dark preference, social preference, object familiarity, and novel object recognition tests.</p> Results <p>HMEMP showed strong, dose-dependent antioxidant activity and contained functional groups linked to neuroprotection. In zebrafish exposed to ZnO NPs, HMEMP significantly improved cognitive, social, and exploratory behaviors. Histological analysis revealed reduced neuroinflammation and tissue degeneration, supporting the extract’s neuroprotective effects against ZnO NP-induced AD-like symptoms.</p> Conclusion <p>HMEMP exhibits strong antioxidant and neuroprotective properties, suggesting its potential to treat AD and other neurodegenerative diseases. Further research is needed to elucidate the specific bioactive compounds and mechanisms involved in its neuroprotective effects.</p> Graphical abstract <p></p>