Isoorientin (ISO), a flavone C-glycoside, is a glycogen synthase kinase 3β (GSK3β) substrate-competitive inhibitor. ISO has potential in treatment of Alzheimer's disease (AD). An excessive activation of GSK3β can lead to neuroinflammation causing neuronal damage. Microglia cells, as resident immune cells of the central nervous system, mediate neuroinflammation. Here, we studied the effects of ISO on microglial activation to alleviate neuroinflammation.