Background Diabetes and malnutrition are common in patients with kidney failure. We aimed to evaluate the postprandial glucose response to oral nutritional supplement drinks (ONSs) in patients with diabetes undergoing hemodialysis treatment. Methods A randomized, single‐blind crossover study was conducted in patients with diabetes, and requiring chronic hemodialysis. Patients consumed either a renal‐specific ONS, macronutrient‐matched ONS, or standard ONS on 3 separate study days, during dialysis, following an overnight fast. Blood was collected before and 15, 30, 45, 60, 90, 120, and 180 minutes post ingestion. Mean net incremental area under the curve (iAUC) and peak incremental blood glucose concentration were compared across conditions, using analyses of variance. Results Consumption of the renal‐specific ONS resulted in the lowest mean net iAUC (87.9 ± 169.0 mmol/L per 3 hours) compared with macronutrient‐matched (188.0 ± 127.5 mmol/L per 3 hours) and standard ONS (199.5 ± 169.2 mmol/L per 3 hours) (F2,30 = 5.115, P = 0.012, partial n2 = 0.254). Pairwise comparisons demonstrated a mean difference of 100.1 mmol/L per 3 hours (95% CI, −2.8 to 202.9) in mean iAUC between the renal‐specific ONS and macronutrient‐matched ONS (P = 0.058). Peak blood glucose concentration, corrected for baseline, was significantly lower after the renal‐specific ONS (1.40 ± 1.0 mmol/L) compared with both macronutrient‐matched (2.02 ± 0.71 mmol/L, P = 0.036) and standard ONS (2.3 ± 1.06 mmol/L, P = 0.017). Conclusion A renal‐specific ONS elicits a lower postprandial glucose response than either macronutrient‐matched ONS or standard ONS in patients with diabetes during hemodialysis.