The structural diversity of NPs reported in NAPROC-13 was analyzed by comparison with FDA-approved drugs and the most diverse set of NPs (UNPD-A), in terms of their distribution of similarity values, computed with the Tanimoto coefficient using four molecular fingerprints: MACCS Keys (166 bits), ECFP4, ECFP6, and MAP4. For NPs in NAPROC-13 and UNPD-A, five random samples of 1000 compounds each were extracted to reduce the computational cost. It has been demonstrated that multiple sampling of 1000 compounds is a valid approach to quantify the entire database pairwise fingerprint-based diversity. Among the multiple methods to perform the molecular scaffold analysis of a set of compounds, we used the definition proposed by Bemis and Murcko, which consists of removing all side chains in molecules and preserving the ring systems and their corresponding linkers. Along with this calculation, scaffold diversity was estimated by computing the scaled Shannon's entropy (SSE) of molecular distribution along the set of presented scaffolds, taking into account the distribution along the first fifteen scaffolds. The Cyclic System Retrieval (CSR) curve was generated as a visual guide to compare the relative scaffold diversity of the databases.