The rapid advancement of computational science continues to drive innovation and create opportunities in the field of drug discovery. With the ongoing expansion of data in the life sciences and the iterative improvement of computational hardware, computational chemistry and cheminformatics have become indispensable tools for researchers in preclinical drug design. This article focuses on two key themes — computer-aided drug design (CADD) and artificial intelligence-driven drug design (AIDD) — to provide a concise overview of the interdisciplinary exploration and innovation at the intersection of computational science and drug discovery, as well as the applications and progress related to preclinical small-molecule drug development.