BACKGROUND/OBJECTIVES: Regulating the postprandial glucose levels is crucial for preventing the progression of prediabetes to diabetes. This study examined the effects of a diabetes-specific nutrition formula (DSNF) on the postprandial plasma glucose, serum insulin, and serum c-peptide levels in individuals with prediabetes. SUBJECTS/METHODS: An open-label, crossover clinical trial was conducted to compare the effects of the DSNF versus standard oral nutritional supplement (ONS) on glycemic control.Fifteen subjects with prediabetes were enrolled and received the DSNF on the first visit and standard ONS on the second. The postprandial plasma glucose, serum insulin, and serum c-peptide incremental area under the curve (iAUC), as well as the incremental maximal concentration (iCmax ) and the maximum concentration (Cmax ), were measured after each intervention. Statistical comparisons between DSNF and standard ONS were conducted using a Wilcoxon’s signed-rank test. RESULTS: After consuming the DSNF, the iAUC of the postprandial glucose level was significantly low compared to the standard ONS (1,683.49 ± 911.65 vs. 4,455.92 ± 1,658.77, P < 0.0001). Similarly, the serum insulin iAUC (2,017.33 ± 987.64 vs. 2,570.59 ± 1,201.09, P = 0.0181) and c-peptide iAUC (274.17 ± 116.12 vs. 491.18 ± 123.90, P < 0.0001) decreased significantly after DSNF administration compared to the standard ONS. CONCLUSIONS The consumption of DSNF significantly improved the postprandial glucose, insulin, and c-peptide responses compared to the standard ONS.