Oxidative stress may play a key role in Alzheimer’s disease (AD) neuropathology. Changes in the oxidative stress, antioxidants, and membrane-bound enzymes were investigated in the cerebral cortex and hippocampus of AD transgenic mice model after long-term dietary supplementation of date palm fruits from Oman. The 4-month-old mice with double Swedish APP mutation (APPsw/Tg2576) were purchased from Taconic Farm, NY, USA; mice were fed two different doses of dates (such as 4 and 2%) or control diet for 15 months and then assessed for the influence of diet on oxidative stress. Significant increase in oxidative stress in terms of enhanced levels of lipid peroxidation (LPO) and protein carbonyls and parallel decrease in the activity of antioxidant enzymes were observed in control diet-treated Tg2576 AD mice. Dates (4 and 2%) treated APPsw/Tg2576 AD mice exhibited significantly attenuated oxidative damage, evidenced by decreased LPO and protein carbonyl levels and restoration in the activities of the antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione, and glutathione reductase). The activities of membrane-bound enzymes (Na+, K+-ATPase and acetyl cholinesterase) were altered in control diet-treated APPsw/Tg2576 AD mice brain regions. Meanwhile, both the percentages of date supplementation were able to restore the activity of enzymes to comparable values observed in controls. In summary, we have shown that chronic dietary supplementation of date palm fruits grown in Oman showed possible beneficial effects concomitant with oxidative stress reduction and increased antioxidant enzymes in AD transgenic mice model. These results warrant further exploration of how anti-reactive oxygen species properties of dates offer such beneficial effects on the AD-like brain.