The development of bacterial resistance to conventional treatments (chiefly antibiotics) has led to the complication of wound infections, thus rendering the search for novel alternative infection-fighting techniques even more urgent. Historically, medicinal plants have been widely used to obtain natural health products, thus, they constitute sources for very promising alternative antibacterial agents against multidrug-resistant (MDR) bacteria. Thus, this study aimed to evaluate the in vitro antibacterial activity of different seed extracts of Silybum marianum against antibiotic-resistant wound infection–causing bacteria (Staphylococcus aureus strain NBRC 100910, Stenotrophomonas maltophilia strain IAM 12423, Klebsiella pneumoniae strain DSM 30104, and Escherichia coli strain NBRC 102203). The most effective extract was selected to investigate its antioxidant potency, assess its effects on the bacterial cell ultrastructure using transmission electron microscopy (TEM), and screen its bioactive components using gas chromatography–mass spectroscopy (GC–MS) analysis. The results indicated that most antibiotics were ineffective against the bacterial isolates; hence, the bacterial isolates were considered to be MDR bacteria. Ethanol extract exhibited the highest inhibition activity against gram-positive and -negative bacteria alongside high antioxidant and antibacterial activities, as revealed by the denaturation and deformation of the ultrastructure of methicillin-resistant S. aureus and S. maltophilia observed via TEM. The GC–MS analysis of ethanol extract revealed the presence of diverse active components with numerous biological activities. Therefore, S. marianum seeds might be promising antioxidant and antibacterial agents against MDR wound infection–causing bacterial strains.