Ganoderma lucidum is known as lingzhi mushroom, which is said to have medicinal properties by the local residents. This research was focused to assess the antidepressant, anxiolytic, and sedative activities of the mentioned mushroom extracts by means of in vivo and in silico approaches. The antidepressant, anxiolytic, and sedative properties of the methanol extracts of G. lucidum (MEGL) were assessed using the forced swim test hole board, open field test, elevated plus maze, hole cross test, and thiopental sodium-induced sleeping time. The extracts revealed significant antidepressant, anxiolytic, and sedative activities in a dose-dependent manner. Rutin and quercetin were found to be the most effective enzyme inhibitors in the molecular docking study. According to the findings of in vivo and molecular docking study, it could be forecast that, the extract could have substantial antidepressant, anxiolytic, and sedative characteristics and deep molecular strategies on this extracts might create a target for the development of novel therapeutics. Further investigations are needed to appraise the molecular mechanisms implicated and isolate the bioactive components.