Background Medicinal mushrooms have a long history of use in traditional medicine and are increasingly investigated in modern oncology as supportive care agents. In recent decades, clinical research has explored their immunomodulatory properties and potential to mitigate chemotherapy-related adverse effects when used as adjuncts to conventional cancer treatment. Objective This review aims to critically evaluate the clinical evidence supporting the use of medicinal mushrooms in oncology, with particular emphasis on immunological modulation, treatment tolerability, safety, and their integration with chemotherapy. Methods A narrative review of clinical trials, cohort studies, systematic reviews, and meta-analyses was conducted. The literature search was conducted in PubMed, Scopus and Google Scholar. Studies published between 2000 to 2026 were considered, Clinical trials, experimental studies and relevant review articles focusing on medicinal mushrooms, chemotherapy and cancer-related mechanisms were included. Mushroom focusing on species with documented clinical evaluation in cancer patients, including Trametes versicolor (L.) Lloyd (Turkey tail), Lentinula edodes (Berk.) Pegler (Shiitake), Grifola frondosa (Dicks.) Gray (Maitake), Ganoderma lucidum (Fr.) Karst. (Reishi), Cordyceps species, Pleurotus species , and selected additional fungi. Outcomes assessed included immune parameters, hematological indices, quality of life, chemotherapy tolerance, and safety. Results Clinical evidence indicates that polysaccharide-rich mushroom extracts exert immunomodulatory effects through interactions with innate immune receptors such as Dectin-1 and complement receptor 3, leading to enhanced natural killer cell activity, improved antigen presentation, and modulation of Th1-associated immune responses. Adjunctive use during chemotherapy is associated with favorable trends in immune preservation, reduced severity of myelosuppression, mitigation of gastrointestinal and systemic inflammatory effects, and improvements in patient-reported quality of life. Serious adverse events are rare, and standardized mushroom preparations demonstrate a favorable safety profile when used appropriately. Conclusion Medicinal mushrooms should be viewed as supportive, rather than cytotoxic, interventions in oncology. When integrated responsibly alongside chemotherapy, selected mushroom extracts may enhance immune resilience, improve treatment tolerability, and support continuity of care. Although evidence is strongest for specific compounds such as PSK and lentinan, further high-quality randomized trials and standardized formulations are required to clarify optimal use and define their role within evidence-based integrative oncology.
Eshed Haklai (Mon,) studied this question.