Split gill mushroom (Schizophyllum commune) compounds reduced Salmonella invasion into human gut cells at doses up to 400 µg/mL while also helping immune cells clear infected bacteria more effectively. Instead of acting like a traditional antibiotic, the mushroom strengthened the body’s own gut defense response by activating macrophages and increasing protective immune signaling. This matters because Salmonella is one of the most common foodborne pathogens worldwide, and antibiotic resistance keeps rising.