It is widely known that the dysregulation of non-coding RNAs (ncRNAs) and dysbiosis of the gut microbiome play significant roles in host development and the progression of various diseases. Emerging evidence has highlighted the bidirectional interplay between ncRNAs and the gut microbiome. This article aims to review the current understanding of the molecular mechanisms underlying the crosstalk between ncRNAs, especially microRNA (miRNA), and the gut microbiome in the context of development and diseases, such as colorectal cancer, inflammatory bowel diseases, neurological disorders, obesity, and cardiovascular disease. Ultimately, this review seeks to provide a foundation for exploring the potential roles of ncRNAs and gut microbiome interactions as biomarkers and therapeutic targets for clinical diagnosis and treatment, such as ncRNA mimics, antisense oligonucleotides, and small-molecule compounds, as well as probiotics, prebiotics, and diets.