Aims: In this study, it was investigated whether the glucose homeostasis is affected by dietary creatine supplementation. For this purpose, the plasma glucose concentration and the plasma insulin response to an oral glucose load were measured in creatine-supplemented vegetarians. Methods: The subjects were supplemented with either 5 g of creatine monohydrate (creatine-treated group, CREAT) or 5 g of maltodextrin (control group, CON) per day for 42 days. On days 0 and 43, blood samples were collected before as well as 10, 20, and 30 min following an oral glucose load and analyzed for plasma creatine, insulin, and glucose levels. Results: Creatine supplementation resulted in an increase in plasma creatine (CREAT 92.7 ± 14.6 µM vs. CON 31.2 ± 3.2 µM; p = 0.001). There was a trend (p = 0.07) towards elevated fasting plasma glucose levels following creatine supplementation, while the plasma glucose response to the glucose load was enhanced (CREAT 168.2 ± 5.3 mM· min vs. CON 129.6 ± 14.7 mM ·min; p = 0.05). There was no difference observed in the plasma insulin response to the glucose load between the groups. Conclusion: This study shows that creatine supplementation may result in abnormalities in glucose homeostasis in the absence of changes in insulin secretion.