Natural sulfur compounds from plants, bacteria, fungi, and animals frequently exhibit interesting biological activities, such as antioxidant, antimicrobial, and anticancer activity. Considering the recent developments in medicine (e.g. oxidative stress in aging, antibiotic resistant bacteria, selective anticancer agents) and agriculture (e.g. ‘green’ pesticides), several of these compounds have become the focus of interdisciplinary research. Among the various sulfur agents isolated to date, polysulfides, such as diallyltrisulfide and diallyltetrasulfide from garlic, are of particular interest, since they combine an unusual chemistry and biochemical mode(s) of action with a distinct biological activity, which includes antimicrobial activity and cytotoxicity against certain cancer cells. In many cases, the biological activity of these compounds is well established, but the underlying causes for this activity are hardly known. As part of our investigations, we have now confirmed the activity of diallyltrisulfide and diallyltetrasulfide against the fairly ‘robust’ Caco-2 colon cancer cell line. At the concentrations used, the activity observed for tri- and tetrasulfide is considerably higher than that of disulfide, while monosulfide is virtually inactive. Controls with the long chain carbon analog 1,9-decadiene count against solely lipophilic effects of diallyltetrasulfide, and together with the ‘ranking’ of activity, point toward a ‘special’ sulfur redox chemistry that emerges when shifting from di- to trisulfide. This special reactivity of polysulfides has previously been associated with certain oxidizing properties of the polysulfides. The electrochemical studies and thiol oxidation assays conducted as part of this study, however, count against the notion of diallyltrisulfide and diallyltetrasulfide as effective oxidants. On the contrary, the rather negative oxidation and reduction potentials associated with these agents point toward a reducing chemistry, which is confirmed in the nitrotetrazolium blue assay: the latter seems to indicate dioxygen reduction to the superoxide radical anion, although other reductive events or H2S release cannot be ruled out at this point. It is therefore likely that diallyltrisulfide and diallyltetrasulfide are reduced inside the cancer cells to perthiols and hydropolysulfides, which in turn trigger a lethal oxidative burst, for instance via superoxide radical anion formation. Further interdisciplinary studies are required to investigate in more detail the rather complicated chemical and biochemical processes, which ultimately may explain the biological activity that is clearly associated with many natural polysulfides.