Alzheimer's disease (AD) is a commonly progressive disorder of dementia. Until now, there are no effective approach to treat the pathological progression of Alzheimer's disease. A novel glucosylated lipids, phosphatidylglucoside (PtdGlc), enriched in the brain, appears to play a important role for brain development. Based on the role of lysoPtdGlc (hydrolytic derivative of PtdGlc)/GPR55-mediated nociceptive afferent axons in the central nervous system, we hypothesized that PtdGlc can aggravated the development of AD. On the contrast, here, we show that long‐term intervention with PtdGlc (0.1% w/w in diet) reduces Aβ and tau pathology, and rescues cognition deficits in APP/PS1 mice. Mechanistically, these improments were linked to the inhibition of APP processing, amelioration of neuroinflammation via the activation of PPARγ, mitigation of oxidative stress, and restoration of the neurotrophin signaling. Our study offers new perspectives for the role of PtdGlc in the Brain, as well as the treatment of AD.