Salmonella entericaserotype Typhi causes chronic enteric fever known as typhoid. Prolonged treatment regimen used for the treatment of typhoid and indiscriminate use of antibiotics has led to the emergence of resistant strains ofS. entericathat has further increased the severity of the disease. Therefore, alternative therapeutic agents are urgently required. In this study, probiotic and enterocin-producing bacteriaEnterococcus faeciumSmr18 was compared for both its prophylactic and therapeutic efficacy inS. entericainfection mouse model.E. faeciumSmr18 possessed high tolerance to bile salts and simulated gastric juice, as treatment for 3 and 2 h resulted in 0.5 and 0.23 log10reduction in the colony forming units, respectively. It exhibited 70% auto aggregation after 24 h of incubation and formed strong biofilms at both pH 5 and 7. Oral administration ofE. faeciumin BALB/c mice infected withS. entericasignificantly (p< 0.05) reduced the mortality of the infected mice and prevented the weight loss in mice. Administration ofE. faeciumprior to infection inhibited the translocation ofS. entericato liver and spleen, whereas, its administration post-infection completely cleared the pathogen from the organs within 8 days. Further, in both pre- and post-E.faecium-treated infected groups, sera levels of liver enzymes were restored back to normal; whereas the levels of creatinine, urea and antioxidant enzymes were significantly (p< 0.05) reduced compared to the untreated-infected group.E. faeciumSmr18 administration significantly increased the sera levels of nitrate by 1.63-fold and 3.22-fold in pre- and post-administration group, respectively. Sera levels of interferon-γ was highest (tenfold) in the untreated-infected group, whereas the levels of interleukin-10 was highest in the post-infectionE. faecium-treated group thereby indicating the resolution of infection in the probiotic-treated group, plausibly due to the increased production of reactive nitrogen intermediates.