Alzheimer's disease (AD) is the most common neurodegenerative disorders of the central nervous system (CNS). Its pathogenesis is complex and needs to be further studied. Recent findings have shown that inflammation, which is characterized by the excessive activation of microglias to produce inflammatory factors, is closely related to the pathogenesis of AD. Improper regulation of microglial receptors and their downstream pathways impair immune homeostasis in AD patients and AD experimental animals. Natural small-molecule compounds reverse the immune imbalance and retard the progresses of AD via inhibting the microglial pro-inflammatory receptors, activating microglial anti-inflammatory receptors and regulating the receptors involved in Aβ clearance. In this paper, we reviewed the mechanisms of chronic inflammation caused by microglias in AD, and summarized the beneficial effects of natural small-molecule compounds in AD immune homeostasis by regulating microglial receptors and their downstream pathways.