Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by cognitive decline and memory impairment. Many lines of evidence indicate that excessive β-amyloid peptide (Aβ) generation and aggregation play pivotal roles in the initiation of AD, leading to various biochemical alteration including oxidative damage, mitochondrial dysfunction, neuroinflammation, signaling pathway and finally resulting in neuronal death. AD has a complex pathogenic mechanism, and a single-target approach for anti-AD strategy is thus full of challenges. To overcome these limitations, the present study focused to review on one of multiple target-compounds, (–)-epigallocatechin-3-gallate (EGCG) for the prevention and treatment of AD. EGCG is a main bioactive polyphenol in green tea and has been reported to exert potent neuroprotective properties in a wide array of both cellular and animal models in AD. This review demonstrated multiple neuroprotective efficacies of EGCG by focusing on the involvement of Aβ-evoked damage and its Aβ regulation. Furthermore, to understand its mechanism of action on the brain, the permeability of the blood-brain barrier was also discussed.