We investigated dendritic polymer effects on brain glial cells: microglia and astrocytes. Microglia are immune cells of the CNS that modulate the activity of astrocytes and production of destructive or protective proteins, including lipocalin-2. We tested dendritic polymers with sulfate terminal groups in both animal models and cultured primary brain cells. We show that a sulfate end group is necessary for polyglycerol dendrimers to exert anti-inflammatory activity and reduce lipocalin-2 production in astrocytes. Sulfated dendritic polyglycerols merit investigations as nanotherapeutics in neurodegenerative disorders associated with inflammation in the brain.