Oligodendrocytes and activated macrophages are involved in the immunopathology of demyelinating disease. In this study, we investigated the in vitro effect of dietary compounds, in particular flavonoids, on oxidative damage in OLN-93 oligodendrocytes and on nitric oxide (NO) production by NR8383 macrophages. Using a cell viability assay, we found the flavonoids luteolin and quercetin to protect OLN-93 cells against hydrogen peroxide-induced oxidative damage. Furthermore, apigenin and luteolin, but not morin inhibited NO production and reduced the expression of inducible NO synthase (iNOS) protein in lipopolysaccharide (LPS)-stimulated NR8383 macrophages. It was found that those dietary compounds effective in preventing oxidative damage in OLN-93 oligodendrocytes were not necessarily effective in reducing NO production and iNOS protein expression in NR8383 macrophages and vice versa. The different properties of the dietary compounds tested in this paper make them potential anti-inflammatory agents targeting neurodegenerative and neuroinflammatory diseases.