<p>Nowadays, there is a rising number of stress-related health problems, such as fatigue, anxiety, and insomnia, which create serious potential threats to the health of physical and mental well-being. Therefore, there is emerging interest in the scientific and clinical community in adaptogenic herbs, or plant agents, that help individuals improve their ability to cope with stress and bring their bodies back to homeostasis. There is growing research literature on the pharmacological effects of seven adaptogenic herbs as part of this review, including <i>Withania somnifera</i> (L.) Dunal, Solanaceae (ashwagandha); <i>Panax ginseng</i> C.A.Mey., Araliaceae; <i>Rhodiola rosea</i> L., Crassulaceae; <i>Eleutherococcus senticosus</i> (Rupr. &amp; Maxim.) Maxim., Araliaceae; <i>Schisandra chinensis</i> (Turcz.) Baill., Schisandraceae; and <i>Glycyrrhiza glabra</i> L., Fabaceae (licorice). A systematic literature search was conducted across multiple databases to summarize the bioactive constituents and empirical clinical research on the adaptogenic mechanism, the modulation of the hypothalamic–pituitary–adrenal axis, and the immune system. The literature suggests that adaptogens demonstrate clinically relevant, significant anti-stress, antioxidant, and immunomodulatory functions for use as supplementary adjuncts in managing stress and optimizing immune function. In summary, we highlight their pharmacological potential and safety and call for continued clinical investigation for future guidelines for clinical utilization in regard to dosing and use.</p> Graphical Abstract <p></p>