Lipoamino acid nanocarriers based on the interactions between L-arginine and oleic acid were formulated with the aid of Tween 80 and explored as a novel carrier for the oral administration of insulin. The interaction between oleic acid and L-arginine was confirmed by FTIR, DSC/TGA, viscosity and surface tension measurements. The pharmacological activity of orally administered insulin-loaded nanocarriers (10, 25 and 50 IU/kg) was evaluated in healthy rabbits. Insulin loaded in lipoamino acid nanocarriers was therapeutically active as demonstrated by the remarkable reduction in blood glucose levels after oral administration of the preparation. A blood glucose lowering of 80% was achieved 4 h after administration of the oral insulin preparation. In addition, insulin-loaded nanocarriers decreased glycemia in a dose dependent manner, with the maximum effect noticed with 50 IU/kg. Moreover, a significant effect observed 1 h after administration suggested that these nanocarriers could be considered as a fast-acting preparation. These results clearly show that these lipoamino acid nanocarriers hold promising potential for oral delivery of insulin.