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[Display omitted] • The effect of adaptogenic herbs on stress was assessed based on a comprehensive systematic search of randomized controlled trials. • Withania somnifera significantly decreases serum cortisol level in mentally stressed healthy adults after 56 or 60 days of treatment. • Withania somnifera clinically relevantly decreases the Perceived Stress Scale score of mentally stressed healthy adults after 56 or 60 days of treatment. • Adaptogens might have an effect on the cortisol pathway and on subjective perception of stress in mentally stressed healthy adults. Stress is a substantial part of life, however, persistent stress can disturb the hypothalamic–pituitary–adrenal axis leading to different diseases. Adaptogenic herbs are considered to have a stress-relieving effect via decreasing cortisol levels. We assessed the effect of adaptogenic plants on cortisol pathway (cortisol and ACTH levels) and on psychological stress levels of mentally stressed healthy adults, based on the results of randomized controlled trials published until June 25th, 2023. Twenty-five studies on nine adaptogenic herbs - Bacopa monnieri, Eleutherococcus senticosus , Eurycoma longifolia , Gynostemma pentaphyllum , Lepidium peruvianum , Ocimum sanctum , Panax ginseng , Rhodiola rosea and Withania somnifera - were processed in the systematic review. The results on Withania somnifera were meta-analyzed. Significant serum cortisol level decrease (MD = -3.27 ug/dL, 95%CI: −4.62––1.92, p = 0.003) and clinically relevant Perceived Stress Scale (PSS) score decrease were observed in the Withania somnifera -treated group compared to the placebo group after 56 or 60 days treatment. [ABSTRACT FROM AUTHOR]