One of the effective methods developed to inhibit the corrosion of steel is the use of organic molecules as corrosion inhibitors. In particular, the design and synthesis of large size organic corrosion inhibitors draws more and more attention. Unfortunately, an atomic-level insight into the inhibition mechanism is still lacking, and regular density functional theory method is found to be inefficient in dealing with large inhibitor-metal adsorption systems. Given this background, in this work, density functional based tight binding (DFTB) approach was used to investigate the adsorption properties of three large size inhibitors (i.e., chalcone derivatives) on an iron surface. The molecular activity of free chalcone derivatives was studied by means of Frontier molecular orbital theory. The growth characteristics of alpha-Fe habits were observed using the "Morphology" software. Some adsorption parameters such as charge density difference, density of states, and changes of molecular orbital were described in detail. The present study is helpful to understand the anticorrosive mechanism of similar organic inhibitors and provides a feasible way to develop novel corrosion inhibitors.