D-mannose, a plant-derived monosaccharide used as a dietary supplement, has shown potential in alleviating obesity symptoms and improving bone loss in mice. Obesity, a known risk factor for osteoporosis (OP), suggests shared molecular pathways between these conditions. This study explores the molecular mechanisms of obesity-induced OP and the potential therapeutic role of mannose supplementation. Using in-silico analysis, GEO2R was applied to dataset GSE110796 to identify differentially expressed genes (DEGs) under high-fat diet-induced obesity and mannose supplementation. Enrichment analysis via Enrichr and ClueGO revealed significant molecular pathways altered by high-fat diets and reversed by mannose. Similarly, pathways for OP were identified using the GEO dataset GSE56815 and DisGeNET-associated genes. Forty-four overlapping pathways were identified between obesity and OP, with key immune and inflammatory pathways modulated by mannose. Notably, genes upregulated in osteoclast differentiation during obesity were downregulated with mannose. These findings suggest that mannose modulates shared pathways in obesity and OP, offering a cost-effective therapeutic approach. This study enhances understanding of obesity-induced OP and provides a foundation for innovative medical interventions.