Esophageal cancer (EC), one highly malignant upper gastrointestinal cancer, is the eighth most commonly occurring cancer and the sixth leading cause of cancer-related deaths worldwide. Clinically, this malignancy is considered to be one of the most difficult-to-treat cancers, owing to its resistance to common therapies like chemotherapy and radiotherapy, and few targeted therapies are available. There is currently an unmet need for treatment of EC. Polyphenols are naturally occurring plant secondary metabolites in response to environmental threats and injury. Epidemiological evidence suggests that long-term consumption of a polyphenol-rich diet is inversely associated with the risk of cancer. Currently, natural polyphenols have received increased attention for their potential therapeutic effects on EC. In this review, we summarize and discuss recent progress in the therapeutic potential of natural polyphenols in EC, as well as their sources, oral bioavailability, and pharmacokinetics. We review natural polyphenols combined with approved chemotherapy and radiotherapy to overcome challenges faced by either monotherapy. We also discuss the current challenges and future directions to accelerate the clinical application of natural polyphenols in EC. We concluded that natural polyphenols represent promising candidates for the management of EC. Well-designed randomized controlled studies are warranted to verify the efficacy and safety of natural polyphenols for EC. Knowledge gained from this review will outline possible future research directions and should help to develop new therapeutics for this disease.