The incidence of leukemia, a malignant cancer originating from the hematopoietic system, is increasing annually. Although traditional treatment method such as chemotherapy and hematopoietic stem cell transplantation have improved patient survival rates to some extent, serious side effects, drug tolerance, and high recurrence rates remain. In recent years, studies have shown that the gut microbiota and its metabolites play an important role in the occurrence, development, and complications of leukemia. Imbalance of the gut microbiota can lead to decreased immune function and an intensified inflammatory response, which is a key factor driving disease progression. Some metabolites, such as short-chain fatty acids, enhance immune function and improve patient prognosis through intestinal barrier repair, while others, such as hydrogen sulfide and bile acids, show potential antitumor effects exerted through regulation of tumor cell apoptosis and immune balance. Traditional Chinese medicine aimed at regulating the structure of the gut microbiota and its metabolites has shown great potential in alleviating the side effects of chemotherapy for leukemia. This review covers the role of the gut microbiota and its metabolites in the occurrence, development, and complications of leukemia, and explores treatment strategies for regulating the microbiota, including fecal microbiota transplantation, probiotics, and traditional Chinese medicine intervention. We anticipate that this review will serve as a reference for improving the treatment and prognosis of leukemia.