For many years, microbiota has been recognized as playing a critical role in the onset and progression of infectious diseases and cancers. In particular, the gut microbiota is known to directly impact the host immune system’s ability to fight off infection and cancer (Yoo et al., 2020). The composition and metabolites of the microbiota have been reported to regulate the maturation of the immune system, modulate the function of immune cells (e.g., CD4+ T cells), and significantly shape the immune response (Levy et al., 2016; Yongbo et al., 2022). Cancer and infection prevention and treatment strategies targeting microbiota and immunomodulation are characterized by high safety and a low risk of severe adverse effects (Jiaao et al., 2025). These approaches can be implemented through various methods, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), antibiotics, traditional Chinese medicine, and others. Preliminary research suggests that microbiota modulation may alleviate these disease (Zhu and Yang, 2025), but further mechanistic insights and more effective therapeutic strategies are still needed. This Research Topic brings together four articles that present and summarize the latest research advances that provide a better understanding of gut microbiota-based immune improvement and safe therapies for the treatment of a wide range of cancers and infectious diseases.