Updated project metadata. Herein, we describe a method, dubbed PROMIS that allows simultaneous, global analysis of endogenous protein–small-molecule and protein-protein complexes. To this end a cell-free native lysate was subjected to size-exclusion chromatography followed by quantitative metabolomic and proteomic analysis. Applying this approach to an extract from Arabidopsis thaliana cell cultures, we could retrieve known protein-protein (PPI) and protein–metabolite (PMI) interactions, validating our strategy.