The use of nanoscale materials as bactericidal agents represents a novel paradigm in the development of therapeutics against drug-resistant pathogenic bacteria. In this paper the antimicrobial activity of a water soluble (gold nanoparticle)–polythiophene (AuNP-PTh) composite against common bacterial pathogens is reported. The nanocomposite is broad-spectrum in its bactericidal activity and exhibits a membrane-directed mode of action on target pathogens. The therapeutic potency of AuNP-PTh is demonstrated by experiments which reveal that the nanocomposite can breach the outer membrane defense barrier of Gram-negative pathogens for subsequent killing by a hydrophobic antibiotic, inhibit the growth of model gastrointestinal pathogens in simulated gastric fluid, and significantly eradicate bacterial biofilms. The high bacterial selectivity and lack of cytotoxicity on human cells augers well for future therapeutic application of the nanocomposite against clinically relevant pathogenic bacteria.