Despite the high value of Portuguese elderberries, recognized for decades by European markets, only a few studies address their beneficial effects at cellular level. Aiming to explore the anti-inflammatory and the cellular antioxidant potential characterized extracts from the three main Portuguese elderberry cultivars (Sabugueiro, Sabugueira, Bastardeira) were used. Lipopolysaccharide-stimulated RAW 264.7 cells pre-exposed to elderberry extracts exhibited dose-dependent inhibition of nitric oxide release, evidencing anti-inflammatory activity. Concerning cellular antioxidant protection, HepG2 and Caco-2 cells pre-exposure to elderberry extracts (50 µg/mL) prevented up-to 90 % of tert-butyl hydroperoxide (t-BOOH)-induced toxicity. In Caco-2 cells, elderberry extracts prevented glutathione depletion, reactive oxygen species production, abnormal morphological changes and DNA fragmentation, in response to t-BOOH oxidative insult. Results demonstrated that elderberries have high potential in reducing cellular oxidative stress as well as in preventing inflammatory processes. Thus, elderberries have high potential as health promoters, acting as functional foods or as sources of nutraceuticals.