Primary osteoporosis(POP) has emerged as a major chronic metabolic bone disease compromising the quality of life in middle-aged and elderly populations. It is pathologically characterized by progressive bone loss, microstructural deterioration, increased bone fragility, and a consequent elevated risk of fracture. This review examines the gut microbiota, considered the "second genome" in maintaining host homeostasis, which actively participates in the regulation of bone metabolism through multiple pathways—including the production of bioactive metabolites, modulation of immune-inflammatory balance, and preservation of intestinal barrier integrity—collectively forming the core regulatory network of the "gut-bone axis." Substances used in medicine and food homology offer a dual advantage, providing both nutritional support and pharmacological intervention. Their mild action and favorable safety profile make them particularly suitable for the long-term management required by chronic diseases. Emerging evidence suggests that these substances exert anti-osteoporotic effects through multi-target and multi-pathway mechanisms, such as remodeling the gut microbiota structure, optimizing the microbial metabolite profile, restoring intestinal barrier function, and regulating bone immune-inflammatory responses. This review systematically examines the intrinsic relationship between the gut microbiota and primary osteoporosis. It summarizes the current research progress and clinical applications of commonly used single-herb medicine-food homology substances and classical compound prescriptions in modulating the gut microbiota to intervene in POP. Finally, future research directions and emerging trends in this field are discussed, aiming to provide a theoretical basis and practical reference for the precision prevention and treatment of primary osteoporosis with traditional Chinese medicine and for the development and application of medicine-food homology resources.