Alzheimer disease (AD) is a progressive dementia affecting a large proportion of the aging population. There is evidence that brain tissue in patients with AD is exposed to oxidative stress during the course of the disease. Hesperetin (Hst) is a natural flavonoid, which has been reported to exert various biological activities such as antioxidant and anti-inflammatory effect. The present study aimed to investigate the effects of hesperetin and nano-hesperetin on neurobehavioral activity and superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx) and catalase (CAT) enzymes activity, malondialdehyde (MDA) and glutathione (GSH) levels in hippocampal area of rats in an experimental model of AD. The AD was induced in animals by intracerebroventricular injection of STZ (icv-STZ) unilaterally. Animals were treated with the Hst and nano-Hst (10, 20 mg/kg body weight), then after three successive weeks, recognition memory was examined (passive avoidance test and novel object recognition test) and antioxidant parameters were evaluated. In our study behavioral testes showed improvement on memory retrieval and recognition memory consolidation. Furthermore the Hst and nano-Hst increased the activity of antioxidant enzymes (SOD, glutathione GPx, GRx and CAT) and GSH levels and decreased MDA in the hippocampal area. These results suggested that Hst and nano-Hst may inhibit STZ-induced oxidative stress, and that it may possess therapeutic potential for the treatment of AD.