Retention of albumin in rosiglitazone treatment and further decrease in microalbuminuria is good indication for diabetic patients. However, the several contradictory reports on its adverse side effects like fluid retention and increase in cardio vascular disease are a matter of concern as it is leading to several ambiguities of rosiglitazone treatment. To reduce cardiovascular side effects of glitazones, antihypertensive drug such as valsartan are employed. Since albumin interaction is an important parameter in pharmacokinetic and drug efficacy, we intended to perform in-vitro experiments on albumin-rosiglitazone/valsartan interaction. Different spectroscopic techniques such as steady state fluorescence, time resolved fluorescence, circular dichroism, dynamic scattering and infrared spectroscopy have been employed to explore the interaction of drug with serum albumin. Stoichiometry of the complex formed between albumin-rosiglitazone was found to increase with increase in temperature suggested self-association of albumin which was confirmed by DLS. Circular dichroism study revealed that the secondary structure of albumin is modified on drug interaction. In silico study suggest that binding rosiglitazone to the BSA site I and II could be the prime reason behind self-association which leads to oligomerisation.