Two new aromatic constituents, an oligolignan named tenuifolignan A (1) and a new phenylpropanoid named tenuiglycerol A (2), were isolated from the roots of Polygala tenuifolia collected in Shandong Province, China. Their structures were established by extensive spectroscopic analysis of HRESIMS and 1D/2D NMR data, and the absolute configuration of 1 was assigned by a combination of DP4+ analysis and calculated ECD data. The inhibitory effects of compounds 1 and 2 on nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells, and their protective effects against corticosterone- and H2O2-induced injury in PC12 cells, were evaluated. The two isolates showed significant anti-neuroinflammatory activity, with NO inhibition rates of 77.0% and 90.5% at 40 μM, respectively. However, no appreciable protective effects were observed in either PC12 injury model.