Abstract: Sweetpotato is an important crop for food, feed and industrial raw materials, playing a critical role in ensuring food security and promoting rural revitalization. However, during production and storage, sweetpotato is susceptible to infection by various pathogens including fungi, bacteria, viruses and nematodes, which leads to reduced yield and quality and has become one of the key factors restricting the development of the sweetpotato industry. Breeding and planting disease-resistant varieties is the most economical and effective strategy for controlling sweetpotato diseases. Traditional disease-resistant breeding relies on phenotypic selection, which is limited by long cycles, low efficiency and complex genetic backgrounds, making it difficult to meet the urgent industrial demand for elite disease-resistant varieties. In recent years, with the development of genomics, transcriptomics and molecular biology technologies, remarkable progress has been made in sweetpotato disease resistance research, including the identification of resistance genes, the dissection of signal transduction mechanisms and the application of molecular breeding. This review summarizes the major diseases of sweetpotato and their impacts, analyzes the resistance performance of nationally registered varieties, and outlines disease resistance-related genes and their regulatory mechanisms. In addition, the applications of molecular markers and QTL mapping, genetic engineering, and gene editing in resistance breeding are reviewed. Finally, the key challenges and future prospects of molecular breeding for disease resistance in sweetpotato are discussed, providing a theoretical basis for the development of resistant cultivars.