Objectives Reactive oxygen species can induce cell apoptosis, and oxidative stress has been implicated in a variety of neurodegenerative disorders. Tomatine, which is a naturally occurring steroidal glycoalkaloid isolated from S olanum cathayanum, has shown potent anti-oxidant properties. Methods In this study, we used the SH- SY5 Y cell line as an in vitro model and investigated the protective effect of tomatine against hydrogen peroxide ( H2O2)-induced neurotoxicity in SH- SY5 Y cells. Key findings Tomatine might inhibit the release of cellular lactate dehydrogenase, increase anti-oxidant enzyme activity and glutathione content, reverse the downregulated protein expression of the brain-derived neurotrophic factor ( BDNF), inhibit expression of Bax and activations of caspase-3 and caspase-9 in H2O2-induced SH- SY5 Y cells. Conclusions Tomatine exerted beneficially neuroprotective effect on H2O2-induced SH- SY5 Y cells, mainly enhancing intracellular anti-oxidant enzyme activity and BDNF expression, inhibiting H2O2-induced oxidative stress as well as expression of Bax and activations of caspase-3 and caspase-9, alleviating H2O2-induced SH- SY5 Y cell injury and cell death. [ABSTRACT FROM AUTHOR]