Sarcandra glabra (Thunb.) Nakai is abundantly artificially cultivated for industrial use as an essential pharmaceutical and chemical raw material in China. In this work, five new meroterpenoids (1–5), along with one analog (6) and six known sesquiterpene dimers (7–12) were isolated from Sarcandra glabra. The chemical structures, including absolute configurations, were deduced by extensive spectroscopic methods combined with quantum mechanical electronic circular dichroism (ECD) and nuclear magnetic resonance (NMR) calculations, Mo₂(OAc)₄-induced ECD experiments, and customizable DP4 + probability analysis. Compounds 1–6 are biogenetically assembled by the cyclization of gentisicacid and monoterpene, featuring a novel 6/6/6 -fused ring system. Compounds 4 and 5 possess significant inhibitory effects on nitric oxide (NO) production against lipopolysaccharide (LPS)-induced microglia (BV2) cells, while compounds 8 and 9 displayed an approximately equal effect to Dexamethasone. The analysis of the protein-protein interaction (PPI) network and molecular docking showed 4 and 5 could play an anti-neuroinflammatory role by regulating heat shock proteins 90AA1 (Hsp90AA1). This study provided evidence for further research and utilization of S. glabra in anti-neuroinflammatory medicinal products.