Polyphenol-rich extracts derived from agricultural by-products exhibit promising antiviral properties. This study evaluated the antiviral potential of extracts from red onion peels, vineyard prunings, olive prunings and chicory leaves against human coronavirus HuCoV-229E. Subcritical water extraction and resin adsorption techniques were applied to produce the extracts. The extracts were further characterised for their bioactive content, and three out of four extracts showed a high polyphenol content (>200 mg/g). The antiviral activity was assessed through viral infectivity and replication inhibition assays in human MRC-5 host cells. The results indicate that chicory leaf and red onion peel extracts demonstrated significant antiviral effects, with effective concentrations (EC) of 61.43 µg/mL and 10.1 µg/mL, respectively. Olive pruning extract exhibited moderate activity, while vineyard pruning extract showed limited efficacy. These findings suggest that polyphenol-rich agricultural by-products could serve as sustainable sources for antiviral agents, warranting further investigation into their mechanisms of action and potential applications against other coronaviruses, including SARS-CoV-2.