Background and aim: Salvia officinalis L. is an important medicinal plant and contains many phytopharmaceuticals including phenolic compounds particularly phenolic acids like rosmarinic acid (RA) and salvianolic acid A and B. Phenolic acids are produced via phenylpropanoid and tyrosine-derived pathways, which are catalyzed by L-phenylalanine ammonia-lyase (PAL) and tyrosine aminotransferase (TAT), respectively. Rosmarinic acid synthase (RAS) condensed the products of the two pathways to form RA. In present study, the effects of silver nanoparticles (SNPs) on biosynthesis of phenolic acids and antioxidative responses were investigated. Material and Method: The uptake, translocation and accumulation of SNPs into the leaves were studied by using ICP-MS and TEM. Then the concentration of photosynthetic pigments, MDA, H2O2, and different antioxidants were evaluated. Also, the effect of SNPs on the content of phenolic acids was evaluated by HPLC. Finally, the activity and mRNA level of three key enzymes involved in RA biosynthesis (PAL, TAT, RAS) were assessed to understand the possible molecular mechanism behind the metabolic response of S. officinalis to different SNPs doses. Results: The LM and TEM photomicrographs confirmed the presence of SNPs in the cell wall and also the penetration of them into the parenchyma cells via leaf epidermis after foliar application. A significant decrease of photosynthetic pigments and increase of cell injury indicators, the activity of enzymatic antioxidants and the content of non-enzymatic antioxidants were observed after exposure to 50 and 100 mg l−1 SNPs. In addition, phenolic compounds generally increased. RA increased more than eightfold at 100 mg l−1 SNPs. The content of RA, salvianolic acid A and B was positively correlated with the activity of PAL and RA synthase, but not with TAT. The activity and expression level of RAS as a key enzyme in the biosynthesis pathway of phenolic acids in S. officinalis were positively correlated with RA.