The contents of some its crucial metabolites tend to decrease when Rhodiola crenulata is cultured under low altitude. Interestingly, an endophyte Phialocephala fortinii showed that it could alleviate this problem.There were 16 151 differential genes including 14 706 up-regulated and 1445 down-regulated uni-genes with significant differences (P < 0.05), and a total of 1432 metabolites exhibited statistically significant (P < 0.05) metabolic differences comprising of 27 different marker metabolites which showed highly significant value's of VIP > 5 and P < 0.01. Results highlight differential regulation of 20 enzymatic genes that are involved in the biosynthesis of five different marker metabolites including acetaldehyde, homocysteine, cyclopropylamine, 1-pyrrolinium and halistanol sulfate.The positive physiological effect of P. fortinii on R. crenulata encompasses differential regulation in carbohydrate metabolism, lipid metabolism and secondary metabolite synthesis. This article is protected by copyright. All rights reserved.