Quercetin is a plant origin phytochemical with several pharmaceutical activities such as antioxidant, immunomodulatory, and anti-inflammatory effects. However, consumption of quercetin is limited due to its low aqueous solubility and poor bioavailability. The aim of the present study was to synthesize silver and gold nanoparticles of quercetin with a view to improve its aqueous phase solubility and investigate the effects on LPS-induced neuroinflammation in BV-2 microglial cells. The average size of silver and gold-quercetin nanoparticles was 53 and 27nm, respectively. Absorption peaks in the UV-Vis spectra were observed at 555 and 405nm for gold and silver-quercetin nanoparticles, respectively. The particle size and mapping of silver and gold-quercetin nanoparticles were also determined using a STEM detector. The inflammatory stimulation of the BV-2 cells with LPS caused an elevated release of proinflammatory prostaglandin, E2, nitric oxide (NO), upregulated cyclooxygenase-2, inducible NO synthase mRNA, and protein levels, which were markedly inhibited by the pretreatment with gold-quercetin nanoparticles (highly soluble in water) without causing any cytotoxic effects. The findings of the present study suggest that the potential of gold-quercetin nanoparticles are much better than quercetin and that gold-quercetin nanoparticles might provide protection against inflammatory neurodegenerative disease via suppression of acute microglial activation.