Head and neck cancer is often resistant to chemotherapy because of cancer stem cells that survive treatment and cause recurrence. This review examined 31 studies on methods to overcome this resistance, finding that natural products like mushrooms (Ganoderma lucidum), plants (sulforaphane from broccoli, curcumin from turmeric), and synthetic compounds can enhance chemotherapy effectiveness when combined with traditional drugs. These approaches work by targeting the specific pathways that allow cancer stem cells to survive, potentially improving treatment outcomes while reducing required drug doses and side effects.