Alzheimer’ s disease (AD) is a neurodegenerative disease characterized by cognitive decline,with neuroinflammation being a key driver. As an important transcription factor, cyclic AMP response element binding protein (CREB) is involved in neuroinflammation, synaptic plasticity, and neuronal survival through regulation of multiple signaling pathways. This article reviews the biological functions of CREB, systematically explains the regulatory mechanisms involved in CREB-mediated signaling pathways in AD related to neuroinflammation, including cAMP / PKA, MAPK/ ERK, and PI3K/ AKT, and summarizes the research progress on CREB agonists of small molecule drugs, natural compounds, and cAMP analogues. Precise CREB regulation may provide a new strategy for AD treatment and provide a theoretical basis for identifying new AD therapeutic targets and drugs. This article reviews the research progress of CREB-mediated neuroinflammation in AD.