Multidrug resistance (MDR) is a major cause of failure in chemotherapy and targeted therapy. In recent years, active components of traditional Chinese medicine (TCM), characterized by their "multi-component, multi-target, and low-toxicity" properties, have shown unique advantages in reversing MDR and enhancing the efficacy of chemotherapy. This review systematically summarizes the key molecular mechanisms of MDR, with a focus on representative active components such as baicalein, curcumin, and tanshinone. These compounds have been shown to inhibit drug efflux pumps, restore apoptotic homeostasis, interfere with DNA repair pathways, and modulate the tumor immune microenvironment. Evidence indicates that these components not only exert independent effects in reversing resistance but also act synergistically with conventional chemotherapeutic agents, significantly improving overall antitumor efficacy. This review provides theoretical support for the application of TCM in MDR research and offers new perspectives for the development and optimization of multi-target combination strategies.

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