Background: Over-the-counter dietary supplements are commonly used by patients undergoing surgical procedures, but their perioperative effects are often incompletely characterized. S-adenosylmethionine (SAMe) is a widely available supplement used for several conditions, yet its potential effects on hemostasis and perioperative bleeding remain poorly understood. Objective: To map the available clinical and mechanistic evidence regarding SAMe, its related metabolic pathways, and potential effects on hemostasis and perioperative bleeding. Methods: We conducted a PRISMA-guided scoping review of PubMed, Google Scholar, Cochrane Library, and ClinicalTrials.gov. Studies evaluating SAMe or related components of one-carbon metabolism in relation to perioperative bleeding, coagulation, platelet function, endothelial function, or other physiologic pathways relevant to hemostasis were considered. Conclusions: No human clinical evidence directly linking SAMe supplementation to perioperative bleeding was identified. Existing literature provides limited mechanistic evidence that SAMe and related one-carbon metabolic pathways may influence physiologic processes relevant to hemostasis, but these findings do not establish an association with surgical bleeding. Further clinical and mechanistic studies are needed to characterize the perioperative safety of SAMe.