Vertebrate cholinesterases and monoamine oxidase (MOA) play key role in the regulation of the cholinergic system. Inhibitions of these enzymes have emerged as promising target for the management of neurological disorders. In the present study, cholinesterase (acetylcholinesterase (Ache) and butyrylcholinesterase (Bche)) and MOA inhibition potential of secondary metabolites from sorghum stem was elucidated using Glide (Schrodinger maestro 2017-1). The results showed that, the phyto-constituents from sorghum stem binds with higher affinity and lower free energy compared to the standard ligand with quercetin, kaempferol and catechin having glide score of -11.667, -10.599 and -10.535 respectively against Ache. Rutin, quercitrin and chlorogenic acid showed glide score of -12.643, -10.124 and -9.043 against Bche while epicatech, quercetin and kaempferol showed glide score of -10.424, -9.830 and -9.804 against monoamine oxidase. Quercetin has lower glide score against the three enzymes compared to prostigmine (standard ligand). These secondary metabolites provide evidence as small molecules in management of neurodegenerative disorders.