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Aims: Alzheimer's disease is considered one of the most prevalent neurodegenerative disorders and dementia is the core symptom of this disease. This study was aimed to test the bioactive compounds produced by endophytic fungus for the inhibition of acetylcholinesterase (AChE) activity and to identify the compound responsible for this activity. Methods and Results: Endophytic fungi were isolated from the medicinal plant Tinospora cordifolia and screened for AChE inhibition and antioxidant activity. The extract of one of the isolates Nigrospora oryzae (GL15) showed maximum AChE inhibition as well as antioxidant activity. The compound responsible for AChE inhibition (fraction 3) was identified as quercetin based on UV, FTIR spectra, HPLC and ESI‐MS analyses. Furthermore, the identification of quercetin in the extract of fraction 3 was confirmed by 1H NMR analysis. This extract showed anti‐dementia‐like activity in scopolamine (SCO) model. The minimal effective dose of the extract of fraction 3 modulated the SCO‐provoked cognitive deficits such as impairments in spatial recognition memory and latency period in Y‐maze test and passive avoidance test, respectively. The SCO‐induced modulation in cholinergic pathway was ameliorated by the extract of N. oryzae in hippocampus, resulting in decrease in AChE activity and restoration of cytoarchitecture of hippocampus. Conclusions: The bioactive compound quercetin produced by N. oryzae may cure the learning and memory shortfalls via AChE‐mediated mechanism in experimental mice. Significance and Impact of the Study: The endophytic fungus N. oryzae serves as a potential source for the bioactive compound quercetin, which plays an important role in the management of Alzheimer's disease. [ABSTRACT FROM AUTHOR]