Galectins, β-galactoside-binding lectins, play multiple roles in the regulation of immune and inflammatory responses. The major galectins expressed in the CNS are galectins 1, 3, 4, 8, and 9. Under normal physiological conditions, galectins maintain CNS homeostasis by participating in neuronal myelination, neuronal stem cell proliferation, and apical vesicle transport in neuronal cells. In neuronal diseases and different experimental neuroinflammatory disease models, galectins may serve as extracellular mediators or intracellular regulators in controlling the inflammatory response or conferring the remodeling capacity in damaged CNS tissues. In general, galectins 1 and 9 attenuate experimental autoimmune encephalomyelitis (a model of multiple sclerosis), while galectin-3 promotes inflammation in this model. In brain ischemic lesions, both galectins 1 and 3 are induced to help neuronal regeneration. The expression of galectin-1 is required for astrocyte-derived neurotrophic factor secretion, and recombinant galectin-1 promotes neuronal regeneration. Galectin-3 promotes microglial cell proliferation and attenuates ischemic damage and neuronal apoptosis after cerebral ischemia. In amyotrophic lateral sclerosis models, galectin-3 is deleterious to neuroregeneration, while intramuscular administration of oxidized galectin-1 can improve neuromuscular disorders. In axotomy and Wallerian degeneration, galectin-3 helps phagocytosis of macrophages to clear degenerate myelin in the injured PNS or CNS. Thus, galectins are important modulators participating in homeostasis of the CNS and neuroinflammation. Continued investigations of the roles of galectins in neuroinflammation promise to provide a better understanding of the mechanism of this process and lead to new therapeutic approaches.