How stimulation of the intestinal microbiota may regulate the health-promoting effects of dietary polyphenols on liver function has not been fully elucidated. Therefore, in this study, we examined whether a combination of fructooligosaccharides (FOSs) and a polyphenol preparation (PP) might stimulate the intestinal microbiota to increase liver levels of polyphenol-derived bioactive compounds. We also investigated how this supplementation affected lipid metabolism and antioxidative status in Wistar rats without diet-induced metabolic disturbances. Addition of FOSs to the diet with the PP (CPF group) considerably reduced the caecal activity of microbial enzymes and elevated the production of short-chain fatty acids, mostly propionic acid. The CPF group exhibited increased relative abundances of caecal bacteria that were able to metabolize polyphenols from the examined preparation. Considerably elevated concentrations of ellagic acid, ellagic acid dimethyl ether glucuronide, 4-hydroxybenzoic acid and methyl cyanidin-3-sophoroside were found in the liver in the CPF group. In addition, hepatic downregulation of HIF1α, AHR and SREBP1c, which are molecular factors that regulate lipid metabolism and antioxidative status, was also found in this group. These changes might explain the considerably reduced levels of fat, triglycerides and lipid peroxidation in the liver in the CPF group. Moreover, the combination of FOSs and the PP considerably elevated the total antioxidant status and activity of superoxide dismutase in the blood. To conclude, stimulation of the intestinal microbial composition and activity with FOSs increased the health-promoting effects of the PP by elevating polyphenolic metabolite levels in the liver and improving lipid metabolism and antioxidative status in healthy rats. Therefore, the combination of FOSs and polyphenols might be a valuable dietary supplement that is able to support preventive healthcare.