Background Reliable annotation remains a major challenge in untargeted LC–MS-based metabolomics, lipidomics, and exposomics. Liquid chromatography–hydrogen/deuterium exchange–mass spectrometry (LC–HDX-MS) provides orthogonal structural information by revealing the number of exchangeable hydrogens within a molecule, thereby supporting functional-group assignment, distinguishing isomeric structures, and reducing false-positive annotations. However, broader adoption of LC–HDX-MS for small-molecule analysis has been limited by the lack of dedicated software for systematic data processing and interpretation. Results We developed ExchangeXplorer, an open-source R/Shiny application for processing and visualizing LC–HDX-MS data from small molecules. The software accepts feature tables generated by MS-DIAL, mzmine, and related workflows, automatically pairs unlabeled and HDX-labeled features, calculates deuterium-induced mass shifts, and exports results for downstream annotation. Additional modules provide visualization of paired MS1 and MS/MS spectra, chromatographic validation using extracted ion chromatograms, estimation of exchangeable hydrogens from molecular structures, and generation of m / z –retention time target lists. Evaluation using 163 reference compounds representing metabolites, lipids, pharmaceuticals, and exposome-related chemicals showed that incorporation of experimentally determined exchangeable-hydrogen counts reduced PubChem isomer candidates by an average of 65%. Application to human plasma and serum datasets further demonstrated utility in complex biological matrices. Significance ExchangeXplorer provides a dedicated framework for integrating HDX-derived information into untargeted LC–MS annotation workflows, improving confidence in small-molecule characterization and reducing candidate-space complexity.