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Non-covalent interactions govern ligand binding specificity and affinity, but existing analysis tools cover a limited set of interaction types, treat metal coordination as a generic contact, and struggle to depict macrocyclic ligands such as heme or cobalamin, leaving comprehensive interaction analysis fragmented across multiple programs. We developed Non-Covalent Interaction Profiler (NCI-Profiler), a free web-based and command-line tool for automated detection and visualization of nine types of protein–ligand non-covalent interactions, including metal coordination and halogen–water–hydrogen (XWH) bridges. NCI-Profiler detects interactions directly from PDB or mmCIF coordinates using literature-derived geometric criteria, without manual structure preparation, and produces interactive 2D diagrams, an in-browser three-dimensional viewer, and downloadable 3D PyMOL sessions, together with structured output files. Its accuracy was validated against 85 literature-annotated complexes and directly compared against PLIP, an established interaction-detection tool, on the same dataset. NCI-Profiler achieved F1-scores of 92–100% for π–π stacking, metal coordination, and water bridges, and 77–83% for the remaining types except hydrophobic contacts (54.8%); it detected literature-confirmed interactions more completely than PLIP in five of nine categories and ran roughly twice as fast. Three case studies further show its expanded coverage can reveal binding-pocket growth vectors, explain structure–activity trends, and distinguish receptor-subtype selectivity. NCI-Profiler is freely available at https://ncip.khu.ac.kr .