Abstract: Buckwheat polyphenols have attracted considerable attention due to their potential in regulating postprandial blood glucose; however, their underlying mechanisms remain unclear. In this study, six cereals-buckwheat, wheat, rice, corn, millet, and quinoa-were selected to analyze their total starch content, amylose content, total polyphenol content, and in vitro glycemic index (GI). The inhibitory activities of their polyphenol extracts against starch-digesting enzymes were evaluated. Additionally, the major polyphenolic compounds in buckwheat were identified using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Missing-component experiments, interaction analysis, and molecular docking simulations were further conducted to elucidate the inhibitory mechanisms of key buckwheat polyphenols. The results indicated that, compared with other cereals, buckwheat exhibited higher amylose and total polyphenol contents but a lower GI value. A significant negative correlation was observed between total polyphenol content and GI value. Among the six cereals, buckwheat polyphenol extracts demonstrated the strongest inhibitory effects on α-amylase and α-glucosidase. Six major polyphenolic compounds were identified in buckwheat, namely rutin, quercetin, kaempferol, hyperoside, caffeic acid, and epicatechin. IC₅₀ analysis and missing-component experiments revealed that rutin contributed most significantly to the inhibition of starch-digesting enzymes. Interaction analysis further uncovered a pronounced synergistic inhibitory effect between rutin and hyperoside. Molecular docking results showed that these polyphenols could stably bind to the active sites of the enzymes through hydrogen bonding, hydrophobic interactions, and π-π stacking interactions, thereby reducing enzymatic activity. Overall, the synergistic effect of rutin and hyperoside may constitute a key mechanism by which buckwheat polyphenols inhibit starch-digesting enzymes. This study provides novel insights into the hypoglycemic potential of buckwheat polyphenols and offers a theoretical foundation for the development of natural functional ingredients aimed at postprandial blood glucose regulation.