MOTIVATION: Organisms within ecological systems often engage in molecular interactions that mediate key biological processes, such as protein-protein interactions involved in host-pathogen recognition and symbiosis. Characterization of these interactions at a molecular level is essential for understanding the mechanistic, evolutionary, and functional basis of interspecies interactions, as well as for informing potential therapeutic interventions. However, progress in this field is significantly impeded by the lack of a comprehensive database of interacting species at molecular resolution and the limited availability of experimental data. RESULTS: We introduce the Interacting Species Database (ISDB), a comprehensive resource that catalogs interspecies interactions, annotated with NCBI taxonomic identifiers, interaction types and known molecular interactions. The ISDB encompasses 858 229 interacting species pairs and 171 713 interspecies protein-protein interactions within 261 287 organisms. ISDB is designed to support researchers in searching for, downloading, and depositing interspecies interaction data, which facilitates the study of ecological dynamics across diverse research domains. AVAILABILITY AND IMPLEMENTATION: The ISDB is available via a web interface (https://www.elhabashylab.org/isdb), open-source code on GitHub (https://github.com/ElhabashyLab/ISDB) under the MIT license and is archived on Zenodo (Version v1.0.1, DOI: 10.5281/zenodo.20162385).