The seed of Zanthoxylum tessmanii is widely used in Nigerian ethnomedicine for the management of inflammatory-related conditions. This study aimed to evaluate the anti-inflammatory and genotoxic potentials of Z. tessmanii seed coat, in order to validate its ethnomedicinal claim. The seed coats were air-dried, de-hulled, and pulverized. The resulting powder was extracted using 95% ethanol, and the extract was subjected to phytochemical screening. Anti-inflammatory activity was assessed through erythrocyte membrane stabilization, anti-denaturation, and anti-tryptic assays. Genotoxicity potential was evaluated using the Allium cepa model. The levels of total soluble sugar, proline, and protein were quantified in A. cepa roots treated with Z. tessmanii extract. The results demonstrated that Z. tessmanii possessed anti-inflammatory activity, as evidenced by its ability to stabilize heat and hypotonic-stressed erythrocytes at low concentrations (0.5 mg/ml), with a gradual increase in percentage membrane stability as the concentration increased. Furthermore, Z. tessmanii exhibited favorable anti-denaturation and anti-tryptic activities compared to diclofenac, across different concentrations tested. Conversely, the mitotic index and total number of dividing cells in A. cepa root tips decreased gradually with increasing concentrations of the ethanolic seed coat extract. Notably, this reduction in mitotic index was accompanied by an increase in the concentrations of total proteinand proline contents and decrease in total sugar in A. cepa roots following exposure. In conclusion, Zanthoxylum tessmanii seed coat contains anti-inflammatory constituents and inhibits the division of cells in A. cepa root meristems at high concentration. There was no genotoxicity potential on the chromosomal structure. The study demonstrated that Z. tessmaniiwhich has been used in Nigeria traditional medicine as remedy for toothache is a good source of anti-inflammatory compounds especially when consumed in moderate quantities.