Abstract: In order to explore the antibacterial effects of traditional Tibetan medicine compound, traditional Chinese medicine and traditional Tibetan medicine on Tibetan yak-derived Salmonella, in this experiment, one strain of Tibetan yak-derived Salmonella H42 was used as the research object; 5 traditional Tibetan medicine compounds, 11 traditional Chinese medicines, and 14 traditional Tibetan medicines were selected. Ultrasonic treatment, decoction concentration and other methods were used to prepare pharmaceutical decoction. The K-B method was used to prepare the drug susceptibility tablets of various drugs to preliminarily detect drug sensitivity. The minimum inhibitory concentrations（MIC） and minimum bactericidal concentrations（MBC） of traditional Chinese medicine and traditional Tibetan medicine were determined by microbroth dilution method. According to the broth dilution chessboard method, the antibacterial effect of the combination of traditional Chinese medicine and traditional Tibetan medicine on the strain was detected. At the same time, some traditional Chinese medicine and traditional Tibetan medicine with good effect were selected for animal protection test and liver and cecum bacterial loading determination test. The results showed that the H42 strain was extremely sensitive to fructus chebulae; it was highly sensitive to Renqing Mangjue, Zuozhu Daxi, cinnamon, radix inulae racemosae; medium sensitive to piper longum, pomegranate, purple bergenia, safflower, dried ginger, garden burnet, coptis atractylodes macrocephala; low sensitive or insensitive to other traditional Chinese and Tibetan medicines; sensitive to amikacin, gentamicin, and ciprofloxacin. The MIC and MBC of Renqing Mangjue and fructus chebulae were both 31.25 mg/mL; the MIC and MBC of Zuozhu Daxi and radix inulae racemosae were both 62.50 mg/mL; the MIC and MBC of garden burnet and goldthread were both 31.25 mg/mL, respectively. The combination of Renqing Mangjue and fructus chebulae had the best effect, with a FICI of 0.5. The mortality rate of mice in the traditional Chinese and Tibetan medicine group was significantly reduced by gavage, with a protection rate of over 50%. After intragastric administration of traditional Chinese and Tibetan medicines, the bacterial loadings in the cecum and liver of mice were significantly or extremely significantly reduced（P＜0.05 or P＜0.01）. The results suggested that traditional Chinese and Tibetan medicines had a good antibacterial effect on Tibetan yak-derived Sarmanella H42, among which Renqing Mangjue, Zuozhu Daxi, garden burnet, coptis, fructus chebulae performed better.