Ethanolic & aqueous extracts of Ocimum sanctum, Tinospora cordifolia, Withania somnifera, Avicennia officinalis, Rhizophora mucronata & Shilajit were included in the present in vitro study. Pepsin was used as a substitute for HIV-protease to evaluate effect of these extracts, as pepsin has great structural and functional similarities with HIV-protease. Pepsin assay could be used for preliminary screening of natural products for probable HIV-protease inhibitory activity. The use of combination antiretroviral therapy has yielded clinical benefits for HIV-infected patients, however, it has also led to adverse metabolic effects such as diabetes & when HIV & diabetes intersect, the treatment regimens required for both diseases can be overwhelming for patients. Hence, these extracts were further evaluated for their antidiabetic effect using alpha-Amylase & alpha-Glucosidase enzymes. O. sanctum, T. cordifolia, R. mucronata & Shilajit exhibited putative HIV-protease inhibitory activitiy. Further, O. sanctum & R. mucronata strongly inhibited alpha-Glucosidase enzyme, whereas, Shilajit potently inhibited both the carbohydrate hydrolyzing enzymes. Thus they showed antidiabetic potential also.