Increasing resistance to antibiotics has led to research into new treatment options. Recent studies suggest the use of plant extracts as an alternative strategy. Feijoa is widely known for its efficacy against a broad spectrum of bacterial pathogens. In this study, the antibacterial activity of methanolic extract and nanosilver of Feijoa fruit (FF-AgNPs) was investigated in BALB/c mice infected with Salmonella enterica serovar Typhimurium (SesT). The antimicrobial effect of Feijoa fruit and FF-AgNPs was evaluated by employing minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against SesT. The efficacy of the treatment in vivo was evaluated in mice by quantifying the viable population of SesT ATCC 14028 purchased from the Iranian Biological Resource Center. Both MIC and MBC results showed a strong bactericidal effect of the Feijoa fruit and its nanosilver against SesT. According to the colony count and weight measurement results of the mice, methanolic extract of Feijoa fruit and FF-AgNPs had acceptable antimicrobial efficacy. Also, none of the mice receiving these agents died, while a high mortality rate was observed in the infected group. Due to the continuous increase in microbial resistance and the importance of pathogenic bacteria in the healthcare system, there is a growing need for the use of complementary agents that possess antimicrobial properties. The findings of the current study suggest that methanolic extract of Feijoa fruit and FF-AgNPs can be considered as a beneficial antibiotic supplements due to their favorable antimicrobial effects.