Respiratory viruses are a major public health problem because of their prevalence and high morbidity rate leading to considerable social and economic implications. Cranberry has therapeutic potential attributed to a comprehensive list of phytochemicals including anthocyanins, flavonols, and unique A-type proanthocyanidins. Soy flavonoids, including isoflavones, have demonstrated anti-viral effects in vitro and in vivo. Recently, it was demonstrated that edible proteins can efficiently sorb and concentrate cranberry polyphenols, including anthocyanins and proanthocyanins, providing greatly stabilized matrices suitable for food products. The combination of cranberry and soy phytoactives may be an effective dietary anti-viral resource. Anti-viral properties of both cranberry juice-enriched and cranberry pomace polyphenol-enriched soy protein isolate (CB-SPI and CBP-SPI) were tested against influenza viruses (H7N1, H5N3, H3N2), Newcastle disease virus and Sendai virus in vitro and in ovo. In our experiments, preincubation with CB-SPI or CBP-SPI resulted in inhibition of virus adsorption to chicken red blood cells and reduction in virus nucleic acid content up to 16-fold, however, CB-SPI and CBP-SPI did not affect hemagglutination. Additionally, CB-SPI and CBP-SPI inhibited viral replication and infectivity more effectively than the commercially available anti-viral drug Amizon. Results suggest CB-SPI and CBP-SPI may have preventative and therapeutic potential against viral infections that cause diseases of the respiratory and gastro-intestinal tract.