In early stage of Alzheimer’s disease, the abnormal immune response is commonly regarded as an important change. Among them, microglia activation is an important regulator of immune response, leading to progressive neuronal damage by releasing neurotoxic products. Therefore, it is a promising new strategy to find drugs that can effectively regulate microglial homeostasis and neuroinflammation in the treatment of AD. Artemisinin has strong anti-inflammatory and immune activities. However, it remains unclear whether artemisinin can help regulate microglial activation, thereby improving AD pathology. In this study, we found that artemisinin can significantly reduce amyloid beta-peptide 1-42 (Aβ1-42) induced increase of nitric oxide, reactive oxygen species and inflammatory factors in BV2 cells. In addition, artemisinin inhibits the migration of microglia and prevents the expansion of inflammatory cascade. Mechanical studies show that artemisinin regulates Toll like receptor 4 (TLR4)/nuclear factor- κ B (NF- κ B) The signal pathway inhibits neuroinflammation and plays a neuroprotective role. In addition, artemisinin inhibits the migration of microglia and prevents the expansion of inflammatory cascade. Mechanical studies show that artemisinin regulates the Toll-like receptor 4 (TLR4)/Nuclear factor-kappa B (NF-κB) signaling pathway to inhibit neuroinflammation and play a neuroprotective role. Similar results were obtained in AD model mice, in which Artemisinin administration attenuated Aβ1-42-induced neuroinflammation and neuronal injury, reversing spatial learning and memory deficits. The anti-inflammatory effect of Artemisinin is also accompanied by the activation of the TLR4/NF-κB signaling pathway in the animal model. Our results show that Artemisinin attenuated Aβ1-42-induced neuroinflammation and neuronal injury by stimulating the TLR4/NF-κB signaling pathway. These findings suggest the potential of Artemisinin as a promising therapeutic agent for AD.