Eight previously undescribed and 15 known components, including six neolignans, two monolignan, three sesquineolignans, three dineolignans, eight phenylpropanoids, and one steroid were identified from the seed testa of Vernicia fordii. Their structures were established based on the comprehensive analysis of NMR and ECD data. The anti-neuroinflammatory effects of the isolates were evaluated through nitrite assays in LPS-induced BV2 cells. As a result, isodiverniciasin A, diverniciasin B, diverniciasin C, isoprincepin, princepin, 3, 3'-bisdemethylpinoresinol, (+)-7-epi-sesamin-dicatechol, isoamericanin A, americanin B, 7S, 8R-americanin D, 4-hydroxyl cinnamic aldehyde, 3-hydroxyl-4-methoxyl cinnamic aldehyde and 24R-6β-hydroxy-24- ethylcholest-4-en-3-one exhibited significant inhibitory effects on nitric oxide (NO) production and isoprincepin, princepin, americanin B, and 4-hydroxyl cinnamic aldehyde suppressed the overexpression of inflammatory cytokines TNF-α, IL-1β, and IL-6 in over-activated microglia. The results suggested that bioactive ingredients from the seed testa of V. fordii can serve as potential therapeutic agents for neurodegenerative diseases.