Gut homeostasis is maintained by dynamic host–microbiota interactions. Recently, miRNAs have emerged as key molecular regulators in the mediation of such interactions. Here, we discuss the role of a host miRNA–microbiome axis in gut homeostasis and colorectal cancer (CRC) and the involvement of diet and microbial metabolites in miRNA-mediated intestinal health. Gut homeostasis is maintained by dynamic host–microbiota interactions. Recently, miRNAs have emerged as key molecular regulators in the mediation of such interactions. Here, we discuss the role of a host miRNA–microbiome axis in gut homeostasis and colorectal cancer (CRC) and the involvement of diet and microbial metabolites in miRNA-mediated intestinal health.