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Drought is a major limiting factor of plant productivity worldwide and its incidence is predicted to increase with climate changing. Endophytes are non-pathogenic plant-associated bacteria that can play an significant role in improving plant tolerance to drought. Here, the effects of Bacillus pumilus (B. pumilus) inoculation on growth, metabolite accumulation and related protein expression, and it's mechanism focusing on antioxidant defense of Glycyrrhiza uralensis Fisch. (G. uralensis) subjected to drought stress were investigated under controlled conditions. Drought stress induced oxidative damage and further decreased growth and secondary metabolites in G. uralensis. Exposure of inoculated plant to drought-stress led to significant increase in total biomass by 34.9%, and in oxygen species and antioxidants while decrease in lipid peroxidation level, compared to non-inoculated plants grown under similar conditions. There was a significant effect of the endophyte on plant metabolism; higher levels of total flavonoids, total polysaccharide and glycyrrhizic acid were recorded in roots of colonized plants compared to non-colonized ones. Furthermore, the expression of HMGR, SQS and beta-AS, key enzymes for glycyrrhizic acid synthesis, significantly increased by B. pumilus inoculation. Taken together, our results indicated that B. pumilus improves G. uralensis growth under drought stress through the modification of antioxidants accumulation and enhances glycyrrhizic acid content by the incremental expression of key enzymes. These results will contribute to the development of a microbial agent to improve the yield and quality of medical plants exposed to environmental stresses.