Climate change will most certainly result in increased drought stress events. Besides, water scarcity is already the abiotic stress most limiting to crop production and this is particularly relevant for drought-sensitive legumes. For example, a moderate level of water deficit can reduce soybean production by approximately 40%. In this context, the objective of this study was to develop a method involving the use of beneficial plant x microorganism interaction in order to reduce the impact of water stress on soybean production. In particular we investigated whether the application of two molecules (thuricin-17 or lipochitooligosaccharides (LCO)) produced by a Plant Growth Promoting Rhizobacteria (PGPR), in association with the inoculation of N2-fixing rhizobacteria Bradyrhizobium japonicum could enhance soybean tolerance to water stress conditions. An experiment was conducted in growth chambers, where soybean plants were grown in association with Bradyrhizobium japonicum. Their responses to thuricin-17 and LCO application were investigated under drought conditions. Cytokinin biosynthesis and nodulation process were both modified in plants subjected to LCO application. This occurred predominantly at the end of the drought period and plants were not more tolerant to drought. On the other hand, the application of thuricin-17 under water stress conditions decreased the negative impact of water stress on plant biomass. We proposed that the mechanism underlying this response involved root ABA mediation, leading to a higher root elongation, and thus increasing water uptake and plant water status. This work is a first step towards the identification of methods environmental friendly, allowing a better crop production under drought conditions.