Proteases regulate cell proliferation, cell growth, biological processes, and overall homeostasis. Several proteases are extensively annotated and well-characterized in pathogenic organisms such as bacteria, parasites, and microbial species as anti-bacterial, anti-parasitic and anti-microbial. Several of these proteins are being explored as viable targets for various drug discovery research in various microbial diseases. Despite multiple studies on pathogen proteases, the comprehensive information on pathogen proteases is scattered or redundant, if available. We have developed a comprehensive and integrative protease database resource, ProtPathDB, for 23 pathogen species distributed among five taxa, Amoebozoa, Apicomplexa, Heteroloblosea, Kinetoplastida and Fungi. ProtPathDB collects and organizes sequences, class division, signal peptides, localization, post-translational modifications, three-dimensional structure and related structural information regarding binding sites, and binding scores of annotated proteases. The ProtPathDB is publicly available at http://bioinfo.icgeb.res.in/ProtPathDB. We believe that the database will be a one-stop resource for integrative and comparative analysis of pathogen proteases to better understand the functions of the microbial proteases and help drug discovery efforts target proteases.