Aim: The present work compares standardized hydro-alcoholic extracts of root and stem parts of Boerhavia erecta L. (Nyctaginaceae), leaves of Plumeria acuminate R. Br. (Apocyanaceae), rhizomes of Alpinia galanga Sw. (Zingiberaceae), whole plant of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae), fruits of Trapa natans L. (Trapaceae) for their in vitro antidiabetic and immunomodulatory activities, commonly used by the Trichigadi tribes (Kotas) of south India for various inflammatory disorders. Materials and Methods: Antidiabetic activity of these herbal extracts was assessed through inhibition of glycosylation of hemoglobin and glucose uptake in yeast cells methods at 50, 100 and 200 μg/mL for 72 h. Their respective immunomodulatory activities were evaluated through preservation of heat and hypotonic induced hemolysis, nitroblue terazolium assay and by inhibition of TNF-α and nitric oxide (NO) production in RAW cell lines. Results: B. erecta has shown least cytotoxicity (CTC50 15.7%) and highest % inhibition of TNF-α (58.1) and NO (45.6), statistically significant (p<0.01) to that of normal control. Also, B. erecta (BE), and P. acuminate (PA) exhibited relatively better IC50 values for TNF-α and NO at a concentration less than their respective CTC50 values. Conclusions: Spectral analysis of chloroform fraction of BE hydro-alcoholic extract established the presence of biologically active molecule in it. Root and stem parts of BE extract not only proved to be safe but also demonstrated relatively better efficacy than other established medicinal herbs in selected immune models, may be due to flavonoids or phenolic groups. Further in vivo studies on active molecule of BE towards antidiabetic and immunomodulatory activity are warranted.