This work describes the in vitro interaction between a lupin seed protein, namely, conglutin gamma, and insulin. The binding to an insulin-immobilized matrix occurs in the pH range from 7.5 to 4.2 and is strongly affected by ionic strength, suggesting that it is driven primarily by electrostatic interactions. The quantitative parameters of the binding were determined by surface plasmon resonance. On the basis of the conditions required for the interaction to take place and the quantitative binding parameters, it appeared that the interaction is specific, despite the fact that the origin of the two protein molecules is completely different. The effect of the oral administration of conglutin gamma on the glycemic levels of rats subjected to glucose overloading was a statistically significant reduction in glycemia comparable to that of metformin, a well-known glucose lowering drug. These findings represent the first molecular evidence of the possible use of a legume protein in the control of glycemia.