The number of patients with diabetes was approximately 463 million worldwide in 2019, with almost 57.6% of this population concentrated in Asia. Asians often develop type 2 diabetes (T2D), even if they are underweight and consume a smaller amount of food. Soft drinks contain large amounts of sweeteners, such as high-fructose corn syrup (HFCS). Excessive intake of HFCS drinks is considered to be one of the causes of T2D. In the present study, we investigated the effect of excessive consumption of HFCS–water on glucose tolerance and obesity under conditions of controlled caloric intake using a mouse model. Three-week-old male ICR mice were divided into two groups and given free access to 10% HFCS–water or deionized water. The caloric intake was adjusted to be the same in both groups using a standard rodent diet. The excess HFCS–water intake did not lead to obesity, but led to impaired glucose tolerance (IGT) due to insulin-secretion defect. It affected glucose and fructose metabolism; for example, it decreased the expression of glucokinases, ketohexokinase, and glucose transporter 2 in the pancreas. These results suggest that excessive consumption of HFCS drinks, such as soft drinks, without a proper diet, induces nonobese IGT due to insulin-secretion defect.