Reishi mushroom (Ganoderma lucidum) produced five new compounds (lucidumones L–P) that significantly inhibited migration of aggressive triple-negative breast cancer cells, with certain compounds working in a dose-dependent manner. These compounds directly slowed movement in MDA-MB-231 cells, a key driver of metastasis and poor survival outcomes. This targets how cancer spreads through the body, not just tumor growth, opening new paths for harder-to-treat cancers.