Several factors directly or indirectly influence the CYP activity. CYP mediated metabolism are likely to be potential candidates for drug interaction.Many drug interactions are a result of induction or inhibition of CYP enzymes. Herbal medicines that modulate intestinal and hepatic CYPs can alter the bioavailability and clearance of co –administered drugs. The diabetic patients have reduced immune system where as Piperine which have significant immunomodulatory activity. Hence, the combination has a beneficial effect in diabetic condition in view of the side effects of pioglitazone.Hence, the combination has a beneficial effect in diabetic condition, but special concern has to be observed in diabetic patients with cardiovascular complications in view of the side effects of pioglitazone. Hence the present investigation warrants further studies to find out the relevance of this interaction in human beings and postulates the exact mechanism involved.