Plasticizers are essential in starch processing and performance enhancement. Literature reports suggest that amide plasticizers outperform polyols in starch plasticization. To explore the influence of amide plasticizer molecular size on starch plasticization, a novel plasticizer, N,N-bis(2-formamidoethyl)-formamide (BFEF), containing three amide groups, was synthesized. Molecular dynamics (MD) simulations were performed to construct three plasticizer/starch/water systems using formamide (FM), ethylenebisformamide (EBF), and BFEF as the plasticizers. The mean square displacement (MSD), radial distribution functions (RDF), and hydrogen bonding energies for each system were calculated to assess the effects of the number and structure of amide groups on starch plasticization. Additionally, thermoplastic starches (TPSs) were prepared with these plasticizers, and their properties were characterized by DMA, XRD, FT-IR, SEM, and mechanical testing. The results show that while an increase in the number of amide groups and molecular size impedes the diffusion of the plasticizer into the starch matrix and weakens the interaction between the plasticizer and starch, the preservation of starch crystallinity in the TPS improves its tensile strength. Specifically, the tensile strength of TPS prepared with BFEF (6.6 MPa) was significantly higher than that of TPS prepared with FM (3.75 MPa).