The drug-resistant strains of Staphylococcus aureus have been considered as one of the serious health threats, which are related to high patient hospitalization rates. Besides, Staphylococcus aureus biofilm formation exhibits a drug-tolerant nature and shows nonspecific resistance against a broad-spectrum of antibiotics. The emergence of drug-resistant bacteria stimulated the development of novel medicines as a strategy to control infections. In this study, we evaluated the antibacterial and anti-biofilm activity of gold-complexed sulfonamides against Staphylococcus aureus strains such as methicillin-resistant S. aureus and clinical isolates. Our data showed that the exposure of gold-complexed sulfonamides promoted a remarkable reduction in the bacterial adhesion. Also, confocal microscopy displayed the effects of the compounds on in the bacterial cell biofilm, revealed that the compounds decreased the biofilm formation. Our results also demonstrated that gold-complexed sulfonamides exhibited potent antibacterial activity against Staphylococcus aureus strains. Besides, all compounds presented a synergic antibacterial activity when were associated with classical antibiotics. Gold-complexed sulfonamide compounds did not promote toxic effects on Caenorhabditis elegans. Thus, our results showed that the coordination of sulfonamide with gold is a promising alternative in the development of safe and active compounds against methicillin-resistant and clinical isolates S. aureus. •Gold-complexed sulfonamides have shown antibacterial and also antibiofilm activity.•The presence of gold allows a more effective antibacterial action of the sulfonamide.•Gold-complexed sulfonamides have synergistic activity with classic antibiotics.•The novel compounds were more effective than SMZ.