With the rapid growth of structural data in the Protein Data Bank, efficient mining and utilization of protein-ligand interaction pattern information from these structures can advance rational drug design. Here, we present SiteMatcher, a web server that integrates a curated repository of protein-ligand interaction motifs from the Protein Data Bank with an automated fragment-grafting engine to facilitate structure-based ligand design. The engine identifies motifs similar to user-defined local protein sites, extracts ligand fragments from these motifs, and merges them─either directly or via suitable linkers─with the seed compound to produce ligands complementary to the target pocket. By leveraging site similarity-based fragment reuse, SiteMatcher helps users explore diverse ligand design strategies efficiently. We hope that SiteMatcher will serve as a practical tool for medicinal chemists. The server is freely available at https://sitematcher.xundrug.cn.