Staphylococcus aureus has a broad virulence capacity and biofilm formation limits the control of wound infections. Paulownia tomentosa Steud. (Paulowniaceae) is a rich source of geranylated phenolics responsible for various bioactivities. Ethanolic extract, chloroform fraction, and three flavonoids showed significant antimicrobial activity. In combination with fusidic acid and mupirocin, synergistic potential was observed. Membrane disruption is partly responsible for the antimicrobial activity of geranylated flavonoids. Selected plant formulations reduced the adhesion of bacteria to the abiotic surface, and also the inhibition of intercellular communication and quorum-sensing was described.