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Abstract The research aimed to evaluate the antioxidative and antibacterial characteristics of aqueous sumac extract on methicillin-resistant Staphylococcus aureus through in-vitro and in-vivo study. Sumac extract has been obtained through the soaking method, and its antioxidant properties were gauged using the DPPH free radical scavenging method. The minimum inhibitory concentration (MIC) of sumac extract was determined on S. aureus obtained from hospitalized patients, as well as an assessment of biofilm-formation and the release of bacterial intracellular compounds. in vivo experimentation involved injecting bacteria (108 cfu/ml) into mice, which subsequently manifested indicators of symptoms of infection, and the number of bacteria within their bloodstream was quantified. The Sumac extract demonstrated strong antioxidant properties at concentrations of 1000 mg/ml. Furthermore, the agar tests for the gram staining, mannitol, coagulase, and DNase revealed that 190 cultured bacteria samples were identified as Staphylococcus aureus. These bacteria were resistant to clindamycin, ciprofloxacin, and methicillin antibiotics, but sensitive to erythromycin and penicillin antibiotics. Additionally, the bacteria displayed significant methicillin resistance and formed a strong biofilm (65.78%). The sumac extract showed a MIC range of 125–1000 µg/ml against Staphylococcus aureus. Treatment with concentrations above the MIC was found to prevent the formation of biofilm and increase the release of bacterial intracellular compounds. Sumac extract led to a decrease in bacterial count in the blood of mice and reduced signs of infection. Sumac extract demonstrated powerful antioxidant and antibacterial effects against resistant microorganisms, suggesting its potential as a promising compound for the treatment of resistant infections in future research.