Background: An edible tuber named Amorphophallus commutatus var. wayanadensis (ACW) is used by the local ethnic communities of Wayanad, India, for hemorrhoids while the health benefits remain unexplored to the scientific community. Objectives: Hence, our study was performed to screen the anti-inflammatory and analgesic activities of ACW. Materials and Methods: Screening for the in vitro anti-inflammatory potential on isolated peritoneal macrophages was performed using nitrite assay, nitroblue tetrazolium assay, tumor necrosis factor (TNF)-α production, and cyclooxygenase (COX) enzyme activity. Carrageenan- and formalin-induced paw edema assays were performed to determine anti-inflammatory potential, while tail immersion assays and acetic acid-induced writhing assays were carried out to explore antinociceptive activity in animal models. Results: Bio-molecular mechanistic investigation to evaluate the in-vitro anti-inflammatory activity confirmed the suppressive effect of MEAC on TNF-α, nitric oxide and COX-2 on lipopolysaccharide stimulated peritoneal macrophages, which benchmarked ACW as a potent medicinal plant against inflammation. Further, the efficacy of methanolic extract of A. commutatus var. wayanadensis (MEAC) as an anti-inflammatory agent in murine anti-inflammatory models was demonstrated by formalin- and carrageenan-induced paw edema assays. Administration of MEAC significantly increased the tail flicking latency in mice and also showed prominent reduction in the number of writhes induced by acetic acid, which establishes the real time application of ACW as an analgesic agent. Conclusion: The vital information regarding in vitro and in vivo action of MEAC provided scientific evidence for its traditional usage for hemorrhoids. Thus, this herbal medicine of ethnic tribes can be translated toward modern medicine for health maintenance and disease prevention.