The increasing incidence of severe adenovirus cases underscores the imperative for efficacious anti-adenovirus medications, given the current absence of targeted therapeutic options. This study explores the potential antiviral effects of the natural product Resveratrol (RSV) on various cell lines, marking the first-time discovery of such properties. The results suggest that RSV suppresses the upregulated pathways (NF-κB, JAK-STAT) triggered by viral infections, with its mechanism contingent upon the presence of the SIRT1 protein. Consequently, RSV mitigates the expression of inflammatory factors (IL-6, IL-8) as detected by ELISA. Subsequently, we elucidate the specific amino acid sites on both RSV and SIRT1 using macromolecular docking and protein docking methodologies. This revelation represents the pioneering elucidation of the mechanism and mode of action of resveratrol as an antiviral agent. These promising results establish the substantial potential of RSV as a therapeutic agent against adenovirus-7. The capacity to proficiently hinder adenovirus-7 replication and demonstrate potent antiviral properties in vitro experiments introduces novel avenues for crafting targeted therapies to combat adenovirus infections.