In this study, the mechanism underlying acetylcholinesterase (AChE) and 5-lipoxygenase (LOX) inhibition by two novel alkaloids, beilschglabrine A and beilschglabrine B, as well as their interaction footprints on the binding pockets were investigated. The results showed that beilschglabrine A and beilschglabrine B inhibit both AChE and LOX in a competitive manner by binding to their active sites thereby interfering with substrate access. The interaction of the alkaloids with the enzymes was favorable and stable with low binding energy values which correlate well with their IC50. The depicted molecular interaction, structure-energetic pattern and binding conformations confirmed that beilschglabrine A is more potent than beilschglabrine B. The differences in the binding pose and potency of the alkaloids is occasioned by an extra methyl moiety on beilschglabrine B. The chemical scaffold of the alkaloids respected Lipinski's rule of five and may be relevant in the development of new anti-inflammatory and anti-neurodegenerative disease drugs acting via AChE and LOX inhibition. © 2019 World Scientific Publishing Company.