Helianthus tuberosusL. (Jerusalem artichoke) produce inulin, a type of fructan, which possesses several biotechnology applications, e.g., sugar syrup, prebiotics, fiber in diabetic food, enabling blood sugar and cholesterol reduction. Drought reduces inulin accumulation in the tubers of Jerusalem artichoke as the plants protect themselves from this stress by induction of stress gene responses, effecting growth reduction. Endophytic bacteria are promising candidates to promote plant growth and yield particularly under abiotic stress. Therefore, three endophytic bacteria with plant growth promoting properties were examined for their ability to improve Jerusalem artichoke growth and yield under both well-watered and drought conditions when inoculated individually or in combinations in pot experiments with 2 factorial random complete block design. The interactions of the endophytic bacteria and plant host determined the differential gene expression in response to drought as revealed by quantitative polymerase chain reaction. Single inoculum of the endophytic bacteria increased the height, weight, root traits, and harvest index of Jerusalem artichoke compared to co-inocula under both well-watered and drought conditions. However, the co-inocula ofRossellomorea aquimarisstrain 3.13 andBacillus velezensisstrain 5.18 proved to be a synergistic combination leading to high inulin accumulation; while the co-inocula ofB.velezensisstrain 5.18 andMicrococcus luteusstrain 4.43 were not beneficial when used in combination. The genes, dehydrin like protein and ethylene responsive element binding factor, were upregulated in the plants inoculated with single inoculum and co-inocula of all endophytic bacteria during drought stress. Moreover, the gene expression of indole-3-acetic acid (IAA) amido synthetase were up-regulated in Jerusalem artichoke inoculated withM.luteusstrain 4.43 during drought stress. The fructan:fructan 1-fructosyltransferase (1-FFT) was also stimulated by the endophytic bacteria particularly in drought condition; the results of this study could explain the relationship between endophytic bacteria and plant host for growth and yield promotion under well-watered and drought conditions.