In this paper, we study the relation between the images of polynomial derivations and their simplicity. We prove that the images of simple Shamsuddin derivations are not Mathieu–Zhao spaces. In addition, we show that the images of some simple derivations in dimension three are not Mathieu-Zhao spaces. Thus, we conjecture that the images of simple derivations in dimension greater than one are not Mathieu–Zhao spaces. We also prove that locally nilpotent derivations are not simple in dimension greater than one.