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To develop functional varieties of Capsicum spp. leaves, 40 genetic resources were collected and extracted with 30% aqueous-fermented ethanol. We investigated the protective effects of extracts from 40 genetic resources of Capsicum spp. on glutamate-induced HT22 and LPS-induced BV2 cells. The results showed that the five extracts exhibited cell-protective activities. We also investigated the anti-inflammatory effects of these five extracts on LPS-induced BV2 cell neuroinflammation and found that 23OM18 exhibited superior anti-inflammatory effects. We further investigated the protective activity and anti-inflammatory mechanisms of 23OM18 in these two cell models. In addition, the profiles of 16 metabolites were compared between the representative accessions and among the five genetic resources using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). The results showed that 23OM18 protected HT22 cells by inhibiting reactive oxygen species generation and regulating the MAPK-JNK signaling pathway, thereby reducing LPS-induced BV2 cell neuroinflammation by regulating the NF-κB and MAPK signaling pathways. Based on these results, 23OM18 has the potential to be developed as a functional food for the treatment of neurodegenerative diseases.