Polygonati Rhizoma, a Chinese medicine often used in the clinic, can irritate the tongue and throat, so it must be processed before use. Polygonati Rhizoma contains a variety of chemical components, with saponins being one of the main active ingredients. Saponins can be highly irritating to human mocous membranes and have toxicity. In this study, total saponins were extracted from raw and processed Polygonati Rhizoma and detected by UPLC-Q-TOF-MS to identify their constituents. A total of 46 saponins were detected in TSRPR(total saponins of raw Polygonati Rhizoma), TSSPR(total saponins of steamed Polygonati Rhizoma) and TSWPR(total saponins of Polygonati Rhizoma steamed in wine). Of these, 9 compounds that were present in TSRPR were not detected in TSSPR and TSWPR. C.elegans was used as a model animal to study the neurotoxic effect and its mechanisms. TSRPR was found to have neurotoxic effects on C.elegans, but TSSPR and TSWPR had no adverse effects on the nematodes. The disappearance of the irritant effect of raw Polygonati Rhizoma after processing might be related to the changes in the composition of saponins, and the main reason might be the structural transformation of saponins. In particular, the sugar chains of some highly irritating saponins may have been removed or highly irritating saponins isomerized into weakly irritating saponins. The mechanisms of neurotoxic effects on C.elegans may include upregulation of ced-3 and egl-1 expression to promote apoptosis, damage to GABAergic and cholinergic neurons, downregulation of the GABA transmitter receptor genes ggr-1 and gab-1, and a decrease in glutamate levels that impairs nerve signal transmission.