Metformin is used clinically to reduce fasting glucose with minimal effects on postprandial glucose. Postmeal exercise reduces postprandial glucose and may offer additional glucose-lowering benefit beyond that of metformin alone, yet controversy exists surrounding exercise and metformin interactions. It is currently unknown how postmeal exercise and metformin monotherapy in combination will affect postprandial glucose. Thus, we examined the independent and combined effects of postmeal exercise and metformin monotherapy on postprandial glucose. A randomized-crossover design was used to assess the influence of postmeal exercise on postprandial glucose excursions in 10 people treated with metformin monotherapy (57 ± 10 yrs, HbA1C = 6.3 ± 0.6%). Each participant completed four conditions: sedentary and postmeal exercise (5 x 10-min bouts of treadmill walking at 60% VO2 max) with metformin, and sedentary and postmeal exercise without metformin. Peak postprandial glucose within a 2-hr time window and 2-hr total area-under the-curve were assessed after a standardized breakfast meal, using continuous glucose monitoring. Postmeal exercise significantly blunted 2-hr peak (p = 0.001) and 2-hr AUC (p = 0.006), with the lowest peak postprandial glucose excursion observed with postmeal exercise and metformin combined (p < 0.05 vs. all other conditions: met/sed: 12 ± 3.4, met/ex: 9.7 ± 2.3, washout/sed: 13.3 ± 3.2, washout/ex: 11.1 ± 3.4 mmol/L). Postmeal exercise and metformin in combination resulted in the lowest peak postprandial glucose excursion compared to either treatment modality alone. Exercise timed to the postprandial phase may be important for optimizing glucose control during metformin monotherapy.