This study firstly investigated the feasibility effect and safety of Ganoderma Lucidum Spore Powder (GLSP) for treating patients with epilepsy.Eighteen eligible patients with epilepsy were included. They all received GLSP treatment for a total of 8 weeks. The primary outcome included weekly seizure frequency. The secondary outcomes consisted of each seizure episode, and quality of life, measured by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), as well as the adverse events (AEs).After treatment, GLSP can significant reduce the weekly seizure frequency, compared with it before the treatment (P = .04). However, GLSP did not exert promising effect in each seizure episode (P = .13), and quality of life, measured by the QOLIE-31 scale (P = .11). Additionally, only minor AEs occurred during the treatment period.The results of this study showed that GLSP may be effective for reducing the weekly seizure frequency. Further studies are still needed to warrant this result.