Abstract: Objective: To improve the contents of various hypoglycemic components in natural mulberry leaves, different fermentation-promoting substances were added to mulberry leaf shoots during their fermentation by means of that drawn on the experience of traditional black tea fermentation process. Method: Based on the single factor experiments, orthogonal optimization test was carried out to determine the optimal addition amount using cellulase, pectinase and tea polyphenols as influencing factors, and the contents of total alkaloids, total flavonoids and total polysaccharides in mulberry leaves as comprehensive evaluation indicators. Results: Compared with natural fermentation, the contents of total alkaloids, total flavonoids and total polysaccharides in mulberry leaves fermented by additives were increased by 61.84%, 45.02% and 28.68%, when the addition amounts of cellulase, pectinase and tea polyphenols were 0.6%, 0.8% and 0.9%, respectively. And their contents were 115.12%, 80.19% and 54.81% higher than those in natural mulberry leaves, respectively. Conclusion: The contents of hypoglycemic components in natural mulberry leaves can be improved by adding substances that promote fermentation, which lays a foundation for its subsequent effective utilization in hypoglycemia.