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Panax notoginseng (Burk.) F. H. is a genuine medicinal material in Yunnan Province. As accessories, P. notoginseng leaves mainly contain protopanaxadiol saponins. The preliminary findings have indicated that P. notoginseng leaves contribute to its significant pharmacological effects and have been administrated to tranquilize and treat cancer and nerve injury. Saponins from P. notoginseng leaves were isolated and purified by different chromatographic methods, and the structures of 1–22 were elucidated mainly through comprehensive analyses of spectroscopic data. Moreover, the SH-SY5Y cells protection bioactivities of all isolated compounds were tested by establishing L-glutamate models for nerve cell injury. As a result, twenty-two saponins, including eight dammarane saponins, namely notoginsenosides SL1-SL8 (1–8), were identified as new compounds, together with fourteen known compounds, namely notoginsenoside NL-A3 (9), ginsenoside Rc (10), gypenoside IX (11), gypenoside XVII (12), notoginsenoside Fc (13), quinquenoside L3 (14), notoginsenoside NL-B1 (15), notoginsenoside NL-C2 (16), notoginsenoside NL-H2 (17), notoginsenoside NL-H1 (18), vina-ginsenoside R13 (19), ginsenoside II (20), majoroside F4 (21), and notoginsenoside LK4 (22). Among them, notoginsenoside SL1 (1), notoginsenoside SL3 (3), notoginsenoside NL-A3 (9), and ginsenoside Rc (10) showed slight protective effects against L-glutamate-induced nerve cell injury (30 µM). [ABSTRACT FROM AUTHOR]