OBJECTIVE: To explore the potential target and pharmacological mechanism of atractylenolide Ⅰ,Ⅱ and Ⅲ in Atractylodes macrocephala, and to provide network pharmacology theoretical clues for further research and development of alicolactone. METHODS: The potential target of atractylenolide Ⅰ,Ⅱ and Ⅲ were screened by pharmacophore matching target server PharmMapper, and STRING platform was adopted to establish protein mutual network and screen key target. Therapeutic targets database was used to explore the function of the target and its relationship with pathways and diseases. Molecular docking server SystemsDock was used to dock the atractylenolide Ⅰ,Ⅱ,and Ⅲ with key targets to verify the affinity of atractylenolide Ⅰ,Ⅱ,and Ⅲ with key targets. RESULTS: Atractylenolide Ⅰ,Ⅱ,and Ⅲ mainly acted on 10 key targets such as MAPK8, CASP3, PPARG, NOS3, HSP90AA1, ESR1, AR, GSK3B, BMP2, prothrombin precursor fragment F2, showing potential pharmacological activity in the treatment of tumor, cardiovascular disease and central nervous system disease. Except that the affinity between atractylenolide Ⅰ and MAPK8 was less than 4.25, the docking scores of atractylenolide Ⅰ,Ⅱ, and Ⅲ with the corresponding target were basically above 4.25, and were valid. CONCLUSIONS: Atractylenolide Ⅰ,Ⅱ, and Ⅲ have the pharmacological mechanism of “multiple targets, multiple pathways, and multiple diseases”.