Little is known about the prevalence of persistent human infections by nontyphoidal Salmonella (NTS). Recently published study results indicate that a small fraction (at least 2.2%) of NTS-infected patients continue to shed Salmonella for an extended period of time (up to years). Despite the recommendation not to use antibiotics for the treatment of uncomplicated NTS-Salmonella infection, little treatment guidance is available. Clinical findings from a NTS-patient indicate that administration of synbiotics (probiotic bacteria plus prebiotic) might be considered as a treatment option. We report data of a patient who was treated with a synbiotic preparation containing nine different probiotic bacteria and the prebiotic fructooligosaccharides (FOS). Starting from day one of the treatment, the patient experienced an improvement of symptoms and was symptom-free at the end of a 10 days treatment course. After finishing the treatment, the stool proved to be Salmonella enterica serovar Typhimurium negative. In vitro pathogenic inhibition studies showed the inhibitory effects of the multistrain synbiotic mixture against S. Typhimurium. Growth of S. Typhimurium was also inhibited by individual bacterial strains making part of the composition of the mixture. However, he inhibitory effects of individual strains varied significantly, with those of Streptococcus thermophilus St-21 and Lactobacillus helveticus SP-27 exhibiting the strongest inhibitory effect. Persistent infections by S. Typhimurium are a severe concern for the affected patients. Besides the symptomatic burden, infected persons are banned from work in certain areas (e.g. food related service). In addition, patients with persistent S. Typhimurium infections are a threat for the public health in general, as they serve as a reservoir for NTS transmission. The findings indicate that treatment with a synbiotic preparation might provide a treatment option for persistent S. Typhimurium infections. More clinical data have to be gathered to confirm the relevance of this potential treatment approach.