Polyphenolic compounds, commonly found in Greek medicinal plants, exhibit promising antiviral and antioxidant properties, making them potential candidates for therapeutic purposes. This study aims to evaluate the antiviral activity of nine selected polyphenols against Dengue virus (DENV) and Yellow Fever virus (YFV) life cycles, alongside their antioxidant capacity determined by the DPPH method and the ABTS assay, and their ability to inhibit DNA strand scission induced by peroxyl radicals. Kaempferol and caffeic acid demonstrated the most potent inhibitory effects on DENV genome replication, while coumaric acid blocked viral entry more effectively. Notably, among the nine compounds, kaempferol exhibited the strongest anti-DENV effect, especially at the level of virus-released infectivity, showing the lowest EC₅₀ (3.55 μΜ) and the highest selectivity index (SI = 25.45). In contrast, none of the compounds showed significant antiviral activity against YFV genome replication. Concomitantly, caffeic acid and kaempferol had the highest radical scavenging activity (DPPH and ABTS assays), highlighting their dual properties. Moreover, DNA scission inhibition assays confirmed the strong antioxidant potential of all tested compounds, with caffeic acid and kaempferol achieving the highest inhibition rate of 98.98% and 97.34% respectively. These findings underscore the potential of specific polyphenols, particularly kaempferol and caffeic acid, as antiviral and antioxidant agents targeting DENV and oxidative stress-related damage.