Due to the high surface area, adjustable surface and pore structures, and excellent biocompatibility, nano- and micro-sized silica have certainly attracted the attention of many researchers in the medical fields. This review focuses on the multifunctional roles of silica in different pharmaceutical formulations including solid preparations, liquid drugs, and advanced drug delivery systems. For traditional solid preparations, it can improve compactibility and flowability, promote disintegration, adjust hygroscopicity, and prevent excessive adhesion. As for liquid drugs and preparations, like volatile oil, ethers, vitamins, and self-emulsifying drug delivery systems, silica with adjustable pore structures is a good adsorbent for solidification. Also, silica with various particle sizes, surface characteristics, pore structure, and surface modification controlled by different synthesis methods has gained wide attention owing to its unparalleled advantages for drug delivery and disease diagnosis. We also collate the latest pharmaceutical applications of silica sorted out by formulations. Finally, we point out the thorny issues for application and survey future trends pertaining to silica in an effort to provide a comprehensive overview of its future development in the medical fields. Graphical Abstract. © 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.