Elderberry extract is effective in treatment of flu. This study aimed to determine the mechanism of action of elderberry and its primary active compound, cyanidin 3-glucoside (cyn 3-glu), against influenza virus. The direct effect was studied via hemagglutination inhibition assay, plaque reduction assay, and flow cytometry analysis. In addition, to assess the indirect immunomodulatory effect, the modulation of pro-inflammatory cytokines was evaluated. Elderberry showed mild inhibitory effect at the early stages of the influenza virus cycle, with considerably stronger effect (therapeutic index of 12 ± 1.3) in the post-infection phase. Our data further support both direct effects of elderberry extract by blocking viral glycoproteins as well as indirect effects by increased expression of IL-6, IL-8, and TNF. Cyn 3-glu despite demonstrating a similar direct mechanism of action (IC50 of0.069 mg/ml) compared to the elderberry juice, did not affect the expression of pro-inflammatory cytokines. Inconclusion, elderberry exhibits multiple modes of therapeutic action against influenza infection.