Supplements from arboreal medicinal mushrooms—lion’s mane (Hericium erinaceus), agarikon (Fomitopsis officinalis), and pink oyster (Pleurotus djamor)—reduced anxiety and depression-like behaviors in rats. The mushrooms improved coping strategies in stress tests, with some effects comparable to fluoxetine, a common antidepressant. Results suggest these fungi act through serotonin, GABA, and anti-inflammatory pathways, highlighting their promise as natural options for stress-related disorders.