Phytomics or metabolomics is analysis of large-scale primary and secondary metabolites of plant extracts and provides very meaningful data to monitor or evaluate cellular function or systems biology. The activity of plant extracts depends on the synergistic/antagonistic effect of different metabolites rather than single active metabolites. Matrix metalloproteinases (MMPs) have an active role in the formation of many diseases. To our knowledge, there is no study on the correlation between the phytomics and MMP inhibitory activity of Achillea millefolium, Achillea filipendulina (Asteraceae), Mentha piperita, and Salvia officinalis (Lamiaceae), (AAMS). Therefore, this study aimed to correlate the metabolomics profiling of AAMS extracts to identify the metabolites responsible for the MMP inhibitory activity based on phytomics data. The AAMS extracts showed a significant MMP inhibitory effect (57.73-92.73%) at different concentrations (25-500 mu g/mL). In order to identify the metabolites responsible for such activities in the extract, the metabolomic profiling of the plants was investigated using gas chromatography-mass spectrometry (GC-MS). After deconvolution and aligning of the chromatograms, 284 metabolites were detected, of which 149 were annotated using retention index libraries. Multivariate analyses results indicated that A. millefolium and A. filipendulina showed similar metabolomic profiles, while M. piperita and S. officinalis differed both from each other and from Achillea species. The correlation analysis was applied to evaluate the correlation between metabolomic levels and MMP inhibitory activities, and 96 metabolites had a negative correlation (r <= -0.70) and 55 had a highly positive correlation (r >= 0.70) with MMP inhibitory activity. This is the first study which revealed that phytomics, plant metabolomics, can be used for activity evaluation and a single metabolite may not be responsible for a specific activity. In conclusion, phytomics can be a more useful tool for the evaluation of the activities than investigating a single metabolite. This new perspective can also provide a better understanding of plant metabolomics and can be easily employed for future research on plant activity. (C) 2019 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.