Gelatin is a protein derived from the partial hydrolysis of collagen. Because of its relatively low cost, availability as a renewable resource, biodegradable and the innocuous degradation products, it has already been widely researched as an important raw material for environment and biomedical applications. Gelatin is differentiated from other proteins by the absence of appreciable internal order and the random configuration of the polypeptide chains. However, there are many hydrogen bonds between the gelatin macromolecules, which reduce the movement of these molecules, so the native gelatin has poor processing ability. Thermoplastic gelatin (TPG) can be obtained by denaturation of the protein in the presence of plasticizers under specific conditions. Polyols are the most widely used plasticizers, such as glycerol, glycol, sorbitol and sugars. It is well-known that the glycerol is considered as one of the best plasticizer for gelatin, but its drawback is that it migrates very rapidly to the polymer materials surface. To find out other alternatives, some plasticizers containing amide groups could be used, such as formamide and acetamide (and the formamide/urea mixture. However, these amide group containing plasticizers are toxic, and would not be allowed in many applications. In the present study, a low molecular weight polyester sintetized in laboratory and glycerol were used as the co-plasticizers. The properties of the TPG were investigated. The chemical changes of the gelatin molecules as the function of low molecular weight polyester content were studied. The aim is to obtain a novel thermoplastic gelatin with the properties of low molecular weight and strong interaction between gelatin and plasticizers. The new properties may have some benefits to prevent ageing, to promote the processability, to adjust the biodegradation speed, and to improve the compatibility and distribution when blended with polyester.