Molecular complexity is a useful property in screening compounds against biological targets and indicates the selectivity in the interaction. Herein we discuss the complexity of studied databases according to topological indexes such as CSP3 and the number of chiral centers, and by the substructure-based approaches of ring quantification. In terms of ring content, molecules of NAPROC-13 had an average of 3.92 (median: 4.00; standard deviation: 1.72), FDA-approved drugs 2.78 (median: 3.00; standard deviation: 2.0), and NPs in UNPD-A 3.10 (median: 3.00; standard deviation: 2.2). These values reinforce the tendency of NPs to have greater complexity, according to the metrics implemented. Also, shows a higher complexity of NPs in NAPROC-13 versus those in UNPD-A. Previous findings show that a higher molecular complexity gives place to a better performance in clinical trials, in conjunction with better bioavailability-related physicochemical properties. These observations suggest a high potential in NAPROC-13 to be a database suitable for virtual screening and lead development and optimization.