A personalized antidiabetic therapy is not yet part of the official guidelines of professional societies for clinical practice. The aim of this study was to evaluate the serum C-peptide and plasma glucose levels in patients with type 2 diabetes mellitus (T2DM) after oral administration of whey proteins. Sixteen overweight T2DM Caucasians with good glycemic control and with preserved fasting serum C-peptide levels (>200 nmol/l) were enrolled in this study. Two oral stimulation tests – one with 75 g of glucose (OGTT) and the other with 75 g of whey proteins (OWIST) – were administered for assessing serum C-peptide and plasma glucose levels in each participant. Both oral tests induced similar pattern of C-peptide secretion, with a peak at 90 min. The serum C-peptide peak concentration was 2.91±0.27 nmol/l in OWIST, which was 22 % lower than in OGTT. Similarly, the C-peptide iAUC0-180 were 32 % lower in the OWIST than in the OGTT (p<0.01). Contrary to OGTT the OWIST did not cause a significant increase of glycemia (p<0.01). Our study showed that the OWIST represents a useful tool in estimation of stimulated serum C-peptide levels in patients with T2DM.