It has been reported that amyloid β peptide, the major component of senile plaques, serves a critical role in the development and progression of Alzheimer's disease (AD) by generating reactive oxygen species (ROS), leading to oxidative stress. The aim of the present study was to investigate the protective effect of Oroxylum indicum (L.) extract against Aβ25‑35‑induced oxidative stress and cell injury using SH‑SY5Y cells as a model, and at exploring the underlying mechanisms. The results revealed that the exposure of cells to 20 µM Aβ25‑35 significantly increased cellular oxidative stress, as evidenced by the increased ROS levels. Aβ25‑35 treatment also increased caspase‑3/7 activity and lactate dehydrogenase (LDH) release, and caused viability loss. Oroxylum indicum treatment not only attenuated the generation of ROS and suppressed caspase‑3/7 activity but also reduced the neurotoxicity of Aβ25‑35 in a concentration‑dependent manner, as evidenced by the increased cell viability and decreased LDH release. Treatment with Oroxylum indicum also increased superoxide dismutase (SOD) and catalase (CAT) activity, increased the phosphorylation of Akt and cAMP‑responsive element binding protein (CREB), and contributed to the upregulation of Bcl‑2 protein. In combination, these results indicated that Oroxylum indicum extract could protect SH‑SY5Y cells against Aβ25‑35‑induced cell injury, at least partly, by inhibiting oxidative stress, increasing SOD and CAT activity, attenuating caspase 3/7 activity and promoting the cell survival pathway, Akt/CREB/Bcl‑2. The approach used in the present study may also be useful for preventing the neurotoxicity induced by Aβ in AD and related neurodegenerative diseases. Further studies investigating the activity of Oroxylum indicum extract in vivo are now required.