The WNT/β-catenin signaling pathway plays a crucial role in tumorigenesis, relapse, metastasis, and drug resistance. Abnormal activation of this pathway is often observed in various cancers, making it a promising target for cancer treatment. This review discusses the therapeutic potential of inhibiting the WNT/β-catenin pathway using pharmacological agents, siRNA, and antibodies. It highlights the recent progress in improving the efficiency of chemotherapy, immunotherapy, gene therapy, and physical therapy by targeting the WNT signaling pathway. The review also classifies FDA-approved drugs and natural products that inhibit the WNT signaling pathway based on their structure and physicochemical properties, and explores their potential mechanisms of action. The findings provide a comprehensive understanding of WNT/β-catenin inhibitors in cancer therapeutics, which will benefit the development of novel inhibitors and the optimal clinical use of WNT signaling-related drugs in synergistic cancer therapy.The WNT/β-catenin signaling pathway plays a crucial role in tumorigenesis, relapse, metastasis, and drug resistance. Abnormal activation of this pathway is often observed in various cancers, making it a promising target for cancer treatment. This review discusses the therapeutic potential of inhibiting the WNT/β-catenin pathway using pharmacological agents, siRNA, and antibodies. It highlights the recent progress in improving the efficiency of chemotherapy, immunotherapy, gene therapy, and physical therapy by targeting the WNT signaling pathway. The review also classifies FDA-approved drugs and natural products that inhibit the WNT signaling pathway based on their structure and physicochemical properties, and explores their potential mechanisms of action. The findings provide a comprehensive understanding of WNT/β-catenin inhibitors in cancer therapeutics, which will benefit the development of novel inhibitors and the optimal clinical use of WNT signaling-related drugs in synergistic cancer therapy.