Objective To review and compare regulatory requirements and compliance considerations for the use of human milk oligosaccharides （HMOs） in food for special medical purposes intended for infants across major jurisdictions， and to appraise the mechanistic and clinical evidence for their application in hydrolyzed protein formulas， focusing on safety and key risk-assessment considerations.Methods Official documents （regulations， standards and accompanying） issued by the Codex Alimentarius Commission （CAC）， the U.S. Food and Drug Administration （FDA）， the European Food Safety Authority （EFSA）， Food Standards Australia New Zealand （FSANZ）， and Chinese regulatory authorities were systematically extracted and analyzed using a structured comparative framework. Simultaneously， relevant literature was retrieved from Web of Science （WoS）， PubMed， and CNKI， with a focus on evidence for HMO functions， as well as their clinical application， safety， and tolerability in hydrolyzed protein-based formulas.Results Notable cross-jurisdictional differences existed in permitted HMO species and combinations， maximum usage levels and the basic for their calculation， scope of use and approval pathways， as well as permitted labeling and claim boundaries. Clinical researches have primarily focused on the effects of HMO supplementation in hydrolyzed formulas on gut microbiome-related outcomes， with generally good tolerability reported. However， clear evidence supporting improvements in clinical endpoints such as infections and allergies remains limited， and long-term follow-up data are scarce.Conclusion HMOs represent a promising direction for optimizing hydrolyzed protein-based food for special medical purposes intended for infants. Future regulatory compliant efforts are， however， required to refine dose-population matching， strengthen long-term safety surveillance， and generate higher-quality clinical evidence， to support precision-nutrition applications and evidence-based regulatory evaluation for infants with special medical needs.