The electron-donating capability (EDC) and the ease of deprotonation (ED) of 26 edaravone derivatives have been evaluated. Their first ionization energies have been used to assess their EDC. Four different approaches to obtain vertical ionization energies were tested, using a set of structurally related compounds. Those based on the electron propagator theory (EPT) were identified as the best ones. In particular, the partial third order (P3) approximation led to the lowest mean unsigned error (MUE = 0.10 eV). Two descriptors were used to evaluate ED: the proton affinity (PA) and the pK(a). It was found that pK(a) values are better descriptors than PA values. Ideal candidates to perform as efficiently as, or even better than, edaravone itself are proposed. The recommendations were based on the simultaneous analyses of EDC and ED, and they should be particularly valid when the electron transfer mechanism plays an important role in the antioxidant activity of the studied compounds.