Salmonella enterica serovar Choleraesuis, a host-adapted pathogen of swine, usually causes septicemia. Lactic acid bacteria (LAB) strains have been widely studied in recent years for their probiotic properties. In this study, a mouse infection model first screened for potential agents against infection, then a pig infection model evaluated effects of LAB strains and herbal plants against infection. Scutellariae radix (SR) and Gardeniae fructus (GF) showed abilities to reduce bacteria shedding and suppressing serum level of TNF- α induced by infection in swine. Bioactivities of SR and GF were enhanced by combining with LAB strains, which alone could speed up the bacteria elimination time in feces and boost immunity of infected pigs. Baicalein and genipin exhibited stronger cytotoxicity than baicalin and geniposide did, as well as prevent Salmonella from invading macrophages. Our study suggests LAB strains as exhibiting multiple functions: preventing infection, enhancing immunity to prepare host defenses against further infection, and adjusting intestinal microbes' enzymatic activity in order to convert herbal compounds to active compounds. The SR/GF-LAB strain mixture holds potential infection-prevention agents supplied as feed additives.