Background <p>Medicinal fungi supplements have gained widespread recognition, increasing off-label use in pediatric populations. However, their safety profile remains inadequately characterized, and the potential for toxic effects, including neurotoxicity, is underrecognized in clinical practice. Here we report a pediatric case of suspected multi-component medicinal fungi supplement-related neurotoxicity, in which the parents were aware that the ingredient was a mushroom for their son’s alternative treatment.</p> Case presentation <p>We report acute neurotoxicity in a 9-year-old boy with prematurity, cerebral palsy, and well-controlled epilepsy presenting with generalized myoclonic seizures, hallucinations, and altered mental status following ingestion of multiple medicinal fungi supplements, including <i>Ganoderma lucidum</i> and <i>Cordyceps sinensis</i>. Comprehensive investigations, including laboratory studies and neuroimaging, excluded infectious, structural, and metabolic etiologies. The temporal relationship between dose escalation of the supplement and symptom onset, combined with resolution upon discontinuation, suggested a supplement-related mechanism.</p> Conclusions <p>This case highlights the potential neurotoxic effects of mushroom supplements containing both <i>Ganoderma lucidum</i> (reishi mushroom) and <i>Cordyceps sinensis</i> in children with underlying neurological disorders. The temporal association between dose escalation and symptom onset, with complete symptom resolution upon discontinuation, suggests a supplement-related mechanism. Given the increasing use of medicinal fungi in complementary medicine, greater clinical vigilance and public awareness of their potential risks are essential.</p>