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The tubers of Dioscorea alata L. are popular nutritional supplement and also used in traditional medicine as anti-inflammatory agent. However, in spite of tremendous ethnopharmacological use, the aerial tubers of D. alata have never been evaluated for any kind of bioactivities. Moreover, the phytochemical profile also remained unexplored. Therefore, the present study was conducted to assess the possible immunomodulatory activities and chemically characterise the aerial tubers of D. alata. Results indicate that D. alata aerial tuber extract (DATE) actively stimulates murine humoral immune response and also modulates phagocytosis and related activities of peritoneal macrophages. Up-regulation of IL-4 and IL-10 levels, and down-regulation of nitric oxide (NO), IL-2, IFN-γ, TNF-α, prostaglandin E2 (PGE2) levels, and cyclooxygenase (COX) activities, provided evidence for its anti-inflammatory potentialities. Several bioactive constituents were identified and quantified using chromatographic methods. The present study, therefore, provided evidence of health benefits on consumption of D. alata aerial tubers.