Abstract: Background and Objective: Starfish has been used to treat gastrointestinal diseases since ancient times. Marine gastric medicine with starfish as the main pharmacodynamic component has been used in the clinic for many years. To explore the pharmacological mechanisms of starfish as a traditional medicine in the treatment of peptic ulcer, this study explored the molecular targets and signal networks of starfish in the treatment of peptic ulcer based on systems pharmacology. Materials and Methods: On basis of the PubChem database and SWISS ADME database, four active compounds from Japanese starfish Aphelasterias japonica were selected for protein targets prediction and 38 potential protein targets were matched for peptic ulcer. Results: Results based on Metascape and ClueGo showed that the pharmacological action of starfish towards peptic ulcer mainly involved in the IL-17 signalling pathway and the process of Helicobacter pylori infecting epithelial cells, Mitogen-Activated Protein Kinases (MAPKs) were the key action targets, such as MAPK1 that could be stably bound by the four active compounds. Conclusion: The mechanisms of starfish treating peptic ulcer involves multiple targets, signalling pathways and biological processes, which provides a theoretical basis for developing marine gastric medicine and a direction for further research.