Regarding the Bemis-Murcko scaffolds and analog series, ChemDiv was also the least diverse, while TocrisScreen, Targetmol, and SelleckChem were the most diverse. Taken together, based on the results of structural diversity, the most diverse library overall (TocrisScreen) should be prioritized for experimental medium-throughput screening. Interestingly, out of the 11 databases analyzed, TocrisScreen was the smallest data set (100 compounds), yet it is the most diverse. In sharp contrast, ChemDiv was the largest data set (27,543 compounds) but is the least structurally diverse. The scaffold content and analog series, analyzed in the context of rings present in currently known compounds with activity against epigenetic targets revealed that the focused libraries have a large potential to expand the epigenetic relevant chemical space. Results of the calculated synthetic accessibility showed that all compound data sets are, in general, feasible to make. For practical applications, the libraries could be acquired first by the chemical vendors but, if needed, could be synthesized in-house. We anticipate that the results of the chemoinformatic characterization discussed in this work will assist research teams in the decision-making process and prioritize what libraries move forward to experimental screening in, for example, a high-throughput screening setting.