Objective: The present study was undertaken to investigate the bioavailability enhancing effect of the natural bioavailability enhancers, piperine and ginger oleoresin on the antiretroviral drug atazanvir in combination with ritonavir. Methods : Sprague-Dawley rats of either sex, were used for the bioavailability studies of ATV and RTV in combination of Piperine. All the drugs were administered orally in the form of suspension to the animals. The bioavailability studies were performed by determination of the drugs concentration in plasma by the HPLC. Results : The bioavailability of atazanvir was found to be significantly increased in combination with piperine and ginger oleoresin. However, piperine has demonstrated better effect as compared to ginger oleoresin in all the groups. Piperine (30 mg/kg) when administered in combination with atazanvir (ATV), has shown to increase the bioavailibility of both the doses of ATV (6.5 mg/250 gm) and ATV (3.25 mg/250 gm) significantly as compared to the conventional doses. Conclusion : Results of the investigation proves a significant bioavailability enhancement effect of piperine and ginger oleo resin on atazanavir in lower doses as well as in the absence of rotinavir. These studies places piperine as a mode of increasing activity of atazanvir.