Objectives The therapeutic effects of commonly used drugs on Salmonella in chicken were compared and the reasonable therapeutic drugs were screened out to avoid the blind use of antibiotics. Methods The compound traditional Chinese medicine formula with heat clearing, detoxification and certain antibacterial and anti-inflammatory properties were optimized. The tests of drug sensitivity and treatment comparison of optimized compound traditional Chinese medicine formula with kanamycin sulfate, enrofloxacin, chloramphenicol, and sulfamethoxazole were carried out. Results The highly sensitive strain against sulfamethoxazole accounted for 86.6%, with a cure rate of 86%. The highly sensitive strains against compound traditional Chinese medicine accounted for 73.4%, with a cure rate of 76%. The proportion of highly sensitive strains against kanamycin sulfate and chloramphenicol was 80% and 76.7%, slightly higher than that of the compound Chinese medicine, with a cure rate of 64% and 66%, lower than that of the compound Chinese medicine group. The proportion of highly sensitive strains against enrofloxacin was 56.7%, with a cure rate of 58%, indicating that the effect is poor. Conclusions It is indicated that the compound Chinese medicine has certain antibacterial and anti-inflammatory effects on Salmonella, and the combination of Chinese and Western medicine has good therapeutic and preventive effects on diseases.