We study the symmetry energy (SE), an important quantity in nuclear physics, in the Witten-Sakai-Sugimoto model and in a much simpler hard-wall model of holographic QCD. The SE is the energy contribution to the nucleus due to having an unequal number of neutrons and protons. Using a homogeneous Ansatz representing smeared instantons and quantizing their isospin, we extract the SE and the proton fraction assuming charge neutrality and beta-equilibrium, using quantization of the isospin zeromode. We also show the equivalence between our method adapted from solitons and the usual way of the isospin controlled by a chemical potential at the holographic boundary. We find that the SE can be well described in the WSS model if we allow for a larger ’t Hooft coupling and lower Kaluza-Klein scale than is normally used in phenomenological fits.