<p>Alzheimer’s disease (AD) is a major cause of dementia, a life-threatening condition for which there is currently no cure. Currently, the treatment of AD focuses on reducing the accumulation of amyloid β-protein (Aβ) and the phosphorylation of Tau proteins (Tau). However, simply reducing pathological features does not completely improve AD. Therefore, there is an urgent need to explore a target that regulates AD-related pathologies and highlights its potential as a novel therapeutic target. Recent studies suggest that oxidative stress, neuroinflammation, autophagy dysfunction, and energy metabolism alterations are associated with the development of AD. Reviewing previous data, we found that AMP-activated protein kinase (AMPK) not only acts as a cellular energy sensor to influence the progression of AD, but also activation of AMPK affects the pathologic processes above. In this review, we provide an update on activating the AMPK pathway with targeting in AD therapy. Finally, research has shown that compounds can activate the AMPK pathway to affect a series of cellular processes and improve AD. We propose that AMPK activation represents a paradigm-shifting strategy for AD therapy by simultaneously targeting multiple pathological cascades, although challenges in isoform-specific activation and brain delivery warrant further investigation.</p>