Meroapplanins A-E (1-5) with a 2,3,4,5-tetrahydropyridine fragment were isolated from the fruiting bodies of Ganoderma applanatum. Their structures were elucidated by comprehensive spectroscopic analyses. Their absolute configurations were established based on the X-ray diffraction, electronic circular dichroism (ECD), and calculated nuclear magnetic resonance (NMR) with DP4+ analysis. A plausible biosynthetic pathway for 1-5 was proposed. Furthermore, compounds 1-5, together with optically pure compounds 1a-4a and 1b-4b, were evaluated for their protective effects in PC12 cells damaged by H2O2. The results showed that 3b had protective activity with a cell viability of 82.58 ± 1.31%, compared with the model group (cell viability: 65.27 ± 1.48%).