IsoMatchMS is an open-source R package for identifying molecular annotations from high resolution MALDI-MS data. Trelliscope displays allow users to quickly sort through results to select interesting annotations for further study in downstream analyses, including differential abundance statistics or mass spectrometry imaging. Overall, IsoMatchMS reduces the time burden for identifying high quality annotations, and is an example of a flexible tool built for multiple biological molecules (e.g., metabolites, intact or digested proteins, lipids). Iso-MatchMS provides a critical first screening effort for MALDI-MS data, but manual verification of annotations in the trelliscope display should still occur as settings are variable.