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The immune system is a complex and fundamental network for organism protection. A minimal unbalance in the host defense system homeostasis can originate severe repercussions in human health. Fundamentally, immune-related diseases can arise from its compromise (immunodeficiency diseases), overactivation against itself (autoimmune diseases) or harmless substances (allergies), and failure of eliminating the harmful agent (chronic inflammation). The notable advances and achievements in the immune system diseases pathophysiology have been allowing for a dramatic improvement of the available treatments. Nevertheless, they present some drawbacks, including the inappropriate benefit/risk ratio. Therefore, there is a strong and urgent need to develop effective therapeutic strategies. Nature is a valuable source of bioactive compounds that can be explored for the development of new drugs. Particularly, plants produce a broad spectrum of secondary metabolites that can be potential prototypes for innovative therapeutic agents. This review describes the immune system and the inflammatory response and examines the current knowledge of eight plants traditionally used as immunomodulatory medicines (Boswellia serrata, Echinacea purpurea, Laurus nobilis, Lavandula angustifolia, Olea europaea, Salvia officinalis, Salvia rosmarinus, and Taraxacum officinale). Moreover, the issues responsible for possible biologic readout inconsistencies (plant species, age, selected organ, developmental stage, growth conditions, geographical location, drying methods, storage conditions, solvent of extraction, and extraction method) will also be discussed. Furthermore, a detailed list of the chemical composition and the immunomodulatory mechanism of action of the bioactive compounds of the selected plant extracts are presented. This review also includes future perspectives and proposes potential new avenues for further investigation. [ABSTRACT FROM AUTHOR]