Background: Nepeta binaludensis Jamzad is a perennial medicinal plant with various pharmacological effects. However, the neuroprotective effects of Nepeta binaludensis extracts have not yet been investigated. This study aimed to examine the effects of N. binaludensis hydro-alcoholic extract (NBE) on oxidative stress markers and apoptosis-related proteins in PC12 cells exposed to oxygen-glucose deprivation/ reperfusion (OGD/R). Methods: PC12 cells were pretreated with NBE (at a concentration range of 10-200 μg/ml) before exposure to the OGD condition for 6 h, followed by a 24 h reoxygenation. Cell viability, the production of the reactive oxygen species (ROS), lipid peroxidation (LPO), and the levels of apoptosis-related proteins were evaluated using MTT, fluorimetry, and western blot analysis, respectively. Results: Survival of the cells preincubated for 6 h with NBE increased to 90.20 ± 15.62% compared with those subjected to OGD/R alone (51.26 ± 7.77 %, p < 0.001). ROS formation was also decreased following incubation with 200 μg/ml of NBE to 125.3 ± 18.38% compared to OGD/R group (356.9 ± 70.48%, p < 0.001). LPO was also suppressed after incubation with NBE to 155.5 ± 21.21% compared to the OGD/R group (260.5 ± 9.727%, p<0.001). NBE restored Bax/Bcl-2 ratio (1.3-fold of control), and cleaved caspase-3 (1.58-fold of control, p < 0.001). Conclusion: These results suggest that NBE may offer neuroprotection properties against OGD/Rinduced toxicity through modulation of oxidative stress and apoptotic responses.