The extensive chemical space provides options of selecting molecules that are unique and diverse to build a truly custom made screening chemical library. Finding the right compound from a high‐throughput screening (HTS) that could be optimized to a drug candidate is no simple task. Selecting meaningful compounds from a multitude of commercially available compounds is critical; over the years Institut Pasteur Korea (IPK), whose mission is to eliminate the global threat of infectious disease, had built a selected chemical library of commercially available and proprietary compounds sensitive to encompass structural diversity aspect. To obtain structural diversity, lead‐like Bemis–Murcko substructures were generated from IPK legacy collections, and those compounds with different Bemis–Murcko substructures were selected. Furthermore, structural fingerprints were used to select diverse subsets of compounds. Based on the analyses of whole structures and substructures, we selected a diverse set to utilize against several infectious diseases models provided at IPK. We implemented a strategic approach to managing the chemical library by taking into consideration the stability of compounds while maintaining compounds integrity. Automated liquid handlers were used to compress and replicate the chemical libraries into various concentrations. Emerging infectious diseases are on the rise and unpredictable in the global health landscape; using unique and carefully selected compounds for screening can make a difference in finding our next drug candidate at IPK.