Background: Avocado is a tree’s fruit (Persea AmericanaMill.) of the Laucaceae family. It was reported that consumption of avocado improved cognitive performance. No study has yet been carried out regarding the properties of avocado oil supplementation on the occurrence of Alzheimer's disease. The objective of the present study was to evaluate the effects of extra-virgin avocado oil on a model of D-galactose-induced Alzheimer's disease in ovariectomized Wistar rats. Methods: To accomplish this, 54 female rats were used, of which 42 were ovariectomized (OVX) and 12 underwent white surgery (SHAM). Fourteen days after surgery, the animals were divided into 9 groups of 6 animals each: SHAM+Veh and OVX+Veh groups receiving the vehicle; SHAM + D-gal and OVX+D-gal groups receiving D-galactose and vehicle; OVX+D-gal+E2V and OVX+D-gal+DNPZ groups receiving D-galactose and reference drugs (estradiol valerate and donepezil respectively) and 3 test groups (OVX+D-gal+AO1; OVX+D-gal+AO2 and OVX+D-gal+AO3) receiving D-galactose each and extra-virgin avocado oil at the doses of 0.25, 0.5 and 1 mL/kg respectively. The treatment was carried out during 70 days during which memory disorders were evaluated using the Object Recognition, Y-Maze and MWM tests. Some biochemical parameters regarding memory function were evaluated on hippocampus homogenate 10%. Isolated brain was fixed in 10% formalin for histological analysis. Results: As results, compared to SHAM+Veh group, deterioration of both non-spatial and spatial memory (short- and long-term) was observed in OVX animals threated with D-galactose. In addition, a significant decrease in relative hippocampal weight (p < 0.001), Ach (p < 0.001), Glu (p < 0.001), GSH (p < 0.001), CAT (p < 0.05), and SOD (p < 0.001) activities, and a significant (p < 0.001) increase in Methylglyoxal, MDA, and NO2-. was noted in OVX+D-gal group. Compared to OVX+D-gal group, the treatment with extra-virgin avocado oil at all tested doses reversed or prevented the negative effects induced by ovariectomy and/or by D-galactose on biochemical and oxidative stress biomarkers. The analysis of hippocampus microarchitecture shows that the extra-virgin avocado oil induced a significant decrease (p < 0.05; p < 0.01; p < 0.001) of neuronal loss in CA1 and CA3 hippocampal region. Conclusions: Taken together, these results suggest that avocado oil possesses neuroprotective properties and can be consumed or supplemented to prevent the onset of Alzheimer's disease.