Five previously undescribed monoterpenoid indole alkaloids were isolated from the roots of Gelsemium elegans. Their structures with absolute configurations were elucidated by HRESIMS, X-ray diffraction, ECD spectra, and molecular modeling. 19,20-Epoxyhumantenine is a humantenine-type alkaloid with an epoxypropyl group at the C-20 position, (4 R)-19-oxo-gelsevirine N 4 -oxide is a gelsemine-related alkaloid, and gelsedethenine is a gelsedine-type alkaloid with a butenyl group at the C-20 position. Moreover, 10,11-dimethoxy- N 1 -demethoxy-gelsemamide is an open-loop indole alkaloid and 11-demethoxy-gelsemazonamide is an aromatic azo-linked dimeric indole alkaloid. Among the five alkaloids, (4 R)-19-oxo-gelsevirine N 4 -oxide and 10,11-dimethoxy- N 1 -demethoxy-gelsemamide exhibited significant inhibitory effects on nitric oxide production in lipopolysaccharide-induced RAW 264.7 macrophage cells, with IC 50 values of 6.18 ± 1.07 and 12.2 ± 1.02 μM, respectively. Five previously undescribed monoterpenoid indole alkaloids were isolated from the roots of Gelsemium elegans. (4 R)-19-oxo-gelsevirine N 4 -oxide and 10,11-dimethoxy- N 1 -demethoxy-gelsemamide exhibited significant NO inhibitory activities. Image 106987 • Five previously undescribed indole alkaloids were isolated from Gelsemium elegans. • One of the five alkaloids is the first nonsymmetric aromatic azo-linked bisindole alkaloid. • Two compounds showed NO inhibitory activities in LPS-induced macrophage cells. [ABSTRACT FROM AUTHOR]