Kidney diseases constitute a worldwide public health problem, contributing to morbidity and mortality. The present study aimed to provide an overview of the published data regarding the potential beneficial effects of polyphenols on major kidney diseases, namely acute kidney injury, chronic kidney disease, diabetic nephropathy, renal cancer, and drug-induced nephrotoxicity. This study consists of a bibliographical review including in vitro and in vivo studies dealing with the effects of individual compounds. An analysis of the polyphenol metabolome in human urine was also conducted to estimate those compounds that are most likely to be responsible for the kidney protective effects of polyphenols. The biological effects of polyphenols can be highly attributed to the modulation of specific signaling cascades including those involved in oxidative stress responses, anti-inflammation processes, and apoptosis. There is increasing evidence that polyphenols afford great potential in renal disease protection. However, this evidence (especially when in vitro studies are involved) should be considered with caution before its clinical translation, particularly due to the unfavorable pharmacokinetics and extensive metabolization that polyphenols undergo in the human body. Future research should consider polyphenols and their metabolites that indeed reach kidney tissues.