This study aimed to evaluate the inhibitory potential of phenolic-rich extracts from selected medicinal plants belonging to the and families against the furin protease enzyme, a key target in viral and oncogenic pathways. Extracts of , , , , , and were prepared using hexane, chloroform, and ethyl acetate. Phenolic compounds were quantified using High-Performance Liquid Chromatography (HPLC). Furin inhibition was assessed spectrophotometrically and analyzed statistically with multivariate approaches. The chloroform extract of exhibited 97.44 ± 0.12% inhibition, while the ethyl acetate extract of showed 97.44 ± 0.08% inhibition. Epicatechin and rutin displayed significant synergistic effects, while naringenin negatively affected inhibition ( < 0.05). Solvent polarity significantly influenced phenolic diversity and biological activity, with ternary combinations showing 33% higher inhibition than single compounds. These findings highlight phenolic blends as promising natural furin inhibitors, with chloroform being optimal for broad-spectrum extraction.