Epidemiological studies have shown that consumption of fruits and vegetables is associated with the prevention of chronic diseases such as cancer and cardiovascular disease. Polyphenols in plants are a versatile group of phytochemicals with many potentially beneficial activities in terms of disease prevention. We recently showed that dietary plant polyphenols, namely, the phenolic acids, modulate expression of an important enzyme in both cellular antioxidant defenses and detoxification of xenobiotics, i.e. phenol sulfotransferases (PST). These enzymes are traditionally known as phase II drug-metabolizing or detoxifying enzymes that facilitate the removal of drugs and other xenobiotics compounds. We showed in vitro that p-hydroxybenzoic acid, gallic acid, gentisic acid, ferulic acid, and p-coumaric acid can increase the activities of both PST-P and PST-M. These phenolic acids also exhibit antioxidant activity as evaluated by ORAC and TEAC assays. Furthermore, in two- And three-compound combinations with other phenolic acids, gallic acid and gentistic acid exhibited synergistic effects in the promotion of PST activities. Moreover, animal models were used to investigate the modulatory effect of phenolic acids on hepatic phase II PST and antioxidant status in vivo, our results suggest that phenolic acids might alter sulfate conjugation and antioxidant capacity in living systems. Evidently, PST is important in phase II detoxifying systems; regulation of intracellular PST gene expression may provide an efficient approach to understanding the chemopreventive mechanisms of dietary compounds.