AbstractScope:Resveratrol (3,5,4′‐trihydroxystilbene) is a phytoalexin shown to possess a multitude of health‐promoting properties in pre‐clinical studies. However, the poor in vivo bioavailability of resveratrol due to its rapid metabolism is being considered as a major obstacle in translating its effects in humans. In this study, we examined the hypothesis that piperine will enhance the pharmacokinetic parameters of resveratrol via inhibiting its glucuronidation, thereby slowing its elimination.Methods and results:Employing a standardized LC/MS assay, we determined the effect of piperine co‐administration with resveratrol on serum levels resveratrol and resveratrol‐3‐O‐β‐D‐glucuronide in C57BL mice. Mice were administered resveratrol (100 mg/kg;oral gavage) or resveratrol (100 mg/kg;oral gavage)+piperine (10 mg/kg;oral gavage), and the serum levels of resveratrol and resveratrol‐3‐O‐β‐D‐glucuronide were analyzed at different times. We found that the degree of exposure (i.e. AUC) to resveratrol was enhanced to 229% and the maximum serum concentration (Cmax) was increased to 1544% with the addition of piperine.Conclusion:Our study demonstrated that piperine significantly improves the in vivo bioavailability of resveratrol. However, further detailed research is needed to study the mechanism of improved bioavailability of resveratrol via its combination with piperine as well as its effect on resveratrol metabolism.