Anticholinesterases are drugs that inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Clinical uses of anticholinesterases include: (a) treatment of myasthenia gravis, (b) reversal of the action of non-depolarizing neuromuscular-blocking drugs used during surgical operations, (c) treatment of glaucoma and management of Alzheimer’s disease (AD). Studies have reported several medicinal properties of V. amygdalina and M. fragrans. However the anticholinesterse inhibitory actions (beneficial in neurodegenerative disorders) of these herbs have not been studied, hence the need for the present study. The leaves of V. amygdalina and seeds of M. fragrans were extracted in water and ethanol using cold extraction. The cholinesterase inhibitory assay of the extracts was done in five test tubes: the first three contained the extracts, the fourth test tube contained neostigmine, while the fifth contained blank (control). All the test tubes (control and tests) were incubated tor 20 mins at room temperature after addition of acetylcholinesterse and acetylthiocholine. Thereafter, Ellman’s spectrophotometric method was used to determine the absorbance at 412 nm wavelength. The phytochemical screening revealed the presence of flavonoids, phenolics and glycosides. Aqueous and ethanolic extracts of the leaves of V. amygdalina had mean change in absorbance of 0.032±0.00 and 0.023±0.01 (64 and 74% AChE inhibition respectively), while aqueous seed extract of M. fragrans had 0.015±0.01 (83% AChE inhibition). There were statistically significant differences (p = 0.01) in the mean change in absorbance per minute in the various test groups. Extracts of leaves of V. amygdalina and seeds of M. fragrans showed significant in vitro acetylcholinesterase inhibitory activities at concentrations used.