Representative silica-based microporous materials include zeolite and sol-gel derived silica. Currently, zeolites are classified into more than 210 types based on their framework structures by the International Zeolite Association (IZA), although it is theoretically predicted that there are over a million possible frameworks. Discoveries of zeolites with new framework structures and/or properties, however, have mainly relied upon (pseudo)serendipity and Edisonian trial-and-error approach. Designed synthesis of zeolites with tailored structures and properties is still very difficult, mainly because of a lack of understanding in their formation, conventionally occurred through a complex series of “black-box” hydrothermal reactions. This limits their uses in emerging applications needing more finely tuned architectures. Here we report our attempts to rationally design organic structure-directing agents for synthesis of microporous silica by a computational calculation. Our calculation is performed in two steps: i) screening by the semi-empirical quantum mechanics (QM) or molecular mechanics (MM) using the GULP program, followed by ii) the more accurate calculation by the QM/MM hybrid method. This talk contains i) design of novel anionic organic structure-directing agents for synthesis of microporous silica and ii) design of cationic organic structure-directing agents for tuning the frameworks and properties of zeolites.