This study was aimed to identify more efficient miglustat analogues with anti-inflammatory activity and selective GBA2 action.The focus was given on multivalent iminosugars, on L enantiomers, and on racemic mixtures composed by D and L enantiomers. The effects of these compounds on inflammatory response and cell toxicity in CF bronchial cells and murine models of lung infection were studied. Nanomolar concentrations of monovalent and multivalent DNJ iminosugars and racemic mixtures of N-alkylated iminosugars produced an anti-inflammatory effect in CF bronchial cells. Combination of low doses of miglustat and its L enantiomer was more potent than miglustat alone and reduced the inflammatory response to P.aeruginosa also in CF primary cells.No toxicity was observed both in vitro and in vivo. Combination of low doses of miglustat and its L enantiomer administered to C57Bl/6NCr mice 24 hours before bacterial inoculum improved the capability to resist P. aeruginosa infection. These results confirm that DNJ iminosugars are effective in reducing the inflammatory response to P. aeruginosa in CF bronchial cells.