Résumé : Polyphenolic compounds are an important part of human diet and regular consumption of fruits, vegetables and tea is associated with reduced risk of cancer. Dietary polyphenols display a vast array of cellular effects but the large number of data published in the literature makes it difficult to determine the main mechanisms of action associated and to identify molecules with original mechanisms. Therefore, there is an increasing demand for more systemic approaches in order to obtain a global insight of the biochemical processes mediated by polyphenols. Here, we used Fourier transform infrared (FTIR) spectroscopy to analyze cancer cells exposed in vitro to 6 polyphenols: 3 natural well documented polyphenols (curcumin, epigallocatechin gallate (EGCG) and quercetin) and 3 synthetic molecules with a very closely related chemical structure. Statistical analyses on FTIR spectra allowed the comparison of global effects of the 6 compounds and evidenced some common or different features in the cell perturbations among natural and synthetic molecules. Interestingly, marked metabolic changes induced by polyphenols closely related from a chemical point of view were identified. Furthermore, many metabolic changes could be detected as early as after 2h incubation with the drugs.