Simple SummaryThe majority of cancer-related deaths are attributed to metastatic tumors, making the inhibition of cancer metastasis a critical challenge in cancer treatment. Resveratrol, a compound first reported in 1997 to have anticancer properties, has shown potential in suppressing cancer metastasis in preclinical studies. Despite these positive results, clinical trials have yielded limited progress so far, highlighting the need to understand the cellular processes and signaling pathways involved in resveratrol’s anticancer activity against metastatic tumors. This review article summarizes the past five years’ research on resveratrol’s potential in cancer prevention or therapy and signaling pathways in inhibiting cancer metastasis and evaluates its bioavailability and toxicity. We also discuss the challenges of using resveratrol as an anticancer drug candidate and the current animal models used for preclinical studies. Overall, this article provides valuable insights into the development of resveratrol as an antimetastatic drug for cancer therapy.AbstractCancer metastasis is a significant challenge in cancer treatment, and most existing drugs are designed to inhibit tumor growth but are often ineffective in treating metastatic cancer, which is the leading cause of cancer-related deaths. Resveratrol, a polyphenol found in grapes, berries, and peanuts, has shown potential in preclinical studies as an anticancer agent to suppress metastasis. However, despite positive results in preclinical studies, little progress has been made in clinical trials. To develop resveratrol as an effective anticancer agent, it is crucial to understand its cellular processes and signaling pathways in tumor metastasis. This review article evaluates the current state and future development strategies of resveratrol to enhance its potency against cancer metastasis within its therapeutic dose. In addition, we critically evaluate the animal models used in preclinical studies for cancer metastasis and discuss novel techniques to accelerate the translation of resveratrol from bench to bedside. The appropriate selection of animal models is vital in determining whether resveratrol can be further developed as an antimetastatic drug in cancer therapy.