Pterostilbene, a dimethyl ester analog of resveratrol, has anti‐inflammatory and antioxidative effects and alters cell proliferation. Tristetraprolin (TTP) promotes the degradation of proinflammatory mediators via binding to adenosine and uridine‐ (AU‐) rich elements (ARE) located in the 3′‐untranslated regions of mRNAs. Here, we utilized pterostilbene 4′‐β‐glucoside (4‐PG), a compound derived from pterostilbene, to investigate whether it has anti‐inflammatory effects on dextran sulfate sodium‐ (DSS‐) induced colitis via TTP enhancement. TTP expression was increased in 4‐PG dose‐ and time‐dependent manners in RAW264.7 cells. The production of proinflammatory cytokine, such as TNF‐α, was reduced by 4‐PG in vitro. To investigate the role of TTP in the anti‐inflammatory effects of 4‐PG, we used DSS–induced colitis in TTP WT and KO mice as models. The expression levels of TTP and proinflammatory cytokines were determined in serum and colon tissue. 4‐PG increased the expression of TTP while suppressing proinflammatory cytokines both in vitro and in vivo. These findings suggest that treatment with 4‐PG mediates the anti‐inflammatory effects of 4‐PG on DSS‐induced colitis via enhancing TTP expression.