Addressing the uncontrolled spread and increase in antibiotic resistance in methicillin-resistant Staphylococcus aureus (MRSA) will require new control strategies, particularly to improve the safety of food. Our results revealed the efficacy of theaflavin-3,3′-digallate (TFBG), which is a novel polyphenol derived from tea, in targeting the key regulatory protein multiple gene regulator A (MgrA) in S. aureus. Through fluorescence anisotropy, we showed that the half maximal inhibitory concentration (IC₅₀) of TFBG was 26.76 μg/mL. TFBG uniquely counters S. aureus by regulating its virulence factors and adhesion processes rather than by killing the bacteria directly. This compound alters the expression of key virulence factors and modulates the transcription levels of genes related to adhesion in S. aureus, ultimately reducing the bacteria’s ability to adhere to fibrinogen and its hemolytic activity. Our assays confirmed that TFBG directly interacts with the MgrA protein in MRSA, and we identified critical binding sites. Our in vivo studies highlighted the potent efficacy of TFBG. TFBG administration is an innovative approach to improve food safety by diminishing MRSA virulence and reducing its pathogenicity.