There is compelling evidence showing that dietary phytochemicals have exhibited pronounced bioactivities in a number of experimental models. In addition, a variety of epidemiological surveys have demonstrated that frequent ingestion of vegetables and fruits, which contain abundant phytochemicals, lowers the risk of onset of some diseases. However, the action mechanisms by which dietary phytochemicals show bioactivity remain to be fully elucidated and a fundamental question is why this class of chemicals has great potential for regulating health. Meanwhile, maintenance and repair of biological proteins by molecular chaperones, such as heat shock proteins, and clearance of abnormal proteins by the ubiquitin-proteasome system and autophagy play central roles in health, some disease prevention, and longevity. Interestingly, several recent studies have revealed that phytochemicals, including curcumin (yellow pigment in turmeric), resveratrol (phytoalexin in grapes), quercetin (general flavonol in onions and others), and isothiocyanates (preferentially present in cruciferous vegetables, such as broccoli and cabbage), are remarkable regulators of protein quality control systems, suggesting that their physiological and biological functions are exerted, at least in part, through activation of such unique mechanisms. This review article highlights recent findings regarding the effects of representative phytochemicals on protein quality control systems and their possible molecular mechanisms.