An experiment was conducted to explore the effect of water deficit on 2S albumin gene expression in Moringa oleifera with a predication of its allergenic reactivity. Drought was applied to 20-day-old plants for 1 month by limiting the irrigation water to half the control level. Soil water content and plant relative water content of drought treatment were about 50 and 70% of control values, respectively at the end of the stress period. Additionally, in relation to the control plants, drought reduced plant height (− 34%), leaf number (− 16%), total plant biomass (− 60%), shoot dry mass (− 37%) and root dry mass (− 21%). Conversely, root/shoot ratio was enhanced due to this stress. Quantitative polymerase chain reaction (qPCR) results revealed that drought enormously reduced 2S albumin gene expression in leaves and roots. Under control conditions, the relative albumin gene expression in roots was about half that of the leaves. Paratope and epitope prediction showed that albumin 31 which is a member of 2S albumin family, has eight cysteine residues and 25% of solvent-exposed regions. This makes albumin 31 a proposed target for food allergy investigations. Our interesting finding was that drought decreased 2S albumin expression in this species. This possibly will lower the allergenic reactivity and could enhance the feed value of M. oleifera for human health.