The use of Kukoamine A and Kukoamine B in the preparation of drugs for the prevention and treatment of sepsis and autoimmune disease is disclosed. Bacterial endotoxin/lipopolysaccaride (LPS) and unmethylated DNA (CpG DNA) of bacteria, the major pathogen-associated molecular patterns in sepsis and autoimmune disease, are specifically targeted, while the disclosed use directionally isolates lead compounds from traditional Chinese medicine. These measures can overcome the major defects of uncertainty of pharmacological material basis and drug targets of extracts and constituents of traditional Chinese medicine. The disclosed use can help in developing a safe, effective and quality controllable drug for prevention and treatment of sepsis and autoimmune disease so as to help solve the present lack of effective drugs in clinical treatment.