Objective: The increase in the number of patients with Alzheimer's disease (AD) has led to numerous problems. The risk of developing AD increases in menopause women. Apigenin and is β-estradiol are effective antioxidant and neuroprotective agents. In order to study the combined effects of them on beta-amyloid plaque formation, memory, and learning in ovariectomized rats, the present study was designed. Methods: Forty-two Wistar rats were randomly assigned into 7 groups; ovariectomized (OVX), OVX + apigenin, OVX + β-estradiol, OVX + apigenin + β-estradiol, vehicle and surgical sham. Treatment was done with apigenin and β-estradiol. The formation of β-amyloid plaques, neuronal density in the hippocampus area, apoptosis, memory, and learning was studied. Results: Findings showed the significant formation of β-amyloid plaques in the (hippocampus) area of OVX animals and memory impairment. Apigenin and β-estradiol significantly reduced the number of β-amyloid plaques, as well as the reduction of symptoms of memory impairment and learning and decreased expression of Caspase-3 in treated animals. Conclusion: Accordingly, the combination of antioxidants with E2 could have more strong therapeutic effects for AD.