Three new alkaloids, hipporidine A (1), hipporidine B (2), and (-)-lobeline N -oxide (3), were discovered from the whole plant of Hippobroma longiflora together with five known compounds (4 - 8). Their 2,6-disubstituted piperidine structures were established based on the HRESIMS, NMR (COSY, HMBC, HSQC, NOESY), and UV spectroscopic data. Hipporidines A (1) and B (2) possess a rare 1,3-oxazinane moiety. Compound 3 is the N -oxide derivative of (-)-lobeline (6). Moreover, the absolute configuration of norlobeline (5) was established by single-crystal X-ray diffraction analysis. Three major secondary metabolites (6 - 8) were evaluated for their neuroprotective effect against paclitaxel-induced neurotoxicity. Consequently, pretreatment with compound 8 at a concentration of 1.0 μM displayed significant attenuation on paclitaxel-damaged neurite outgrowth of dorsal root ganglion neurons without interfering with the cytotoxicity of paclitaxel on cervical cancer SiHa cells. © 2023 Georg Thieme Verlag. All rights reserved.