<p>Therapeutic approaches for treating inborn abnormalities by modifying the gut microbiome have recently received new focus on diseases. Inborn errors of metabolism (IEMs), which are monogenic inherited metabolic disorders, represent a significant category of conditions characterised by various neurological symptoms in humans. The gut microbiome contains trillions of microorganisms and has emerged as a dynamic and metabolically active ecosystem, playing critical roles in host physiology, digestion, nutrient metabolism, vitamin synthesis, immune system modulation, and neuronal regulation. This narrative review will examine the complex interaction between gut microbiome dysbiosis and specific IEMs, including congenital hypothyroidism, congenital adrenal hyperplasia, cystic fibrosis, phenylketonuria, biotinidase deficiency, galactosemia, and G6PD deficiency. Previous studies on the importance of manipulating the microbiome and IEM disorders are scarce. We will also discuss the interrelation between the microbiome and a few IEM treatment strategies and explain the role of future therapeutic development in controlling IEM disorders. Additionally, this review article looks closely at the possible benefits of strategies that change the microbiome, like specific diet changes, probiotics, prebiotics, and customised advanced therapies. In conclusion, harnessing the inner ecosystem of the human gut microbiome offers a compelling and innovative avenue for improving the management and outcomes for individuals affected by inborn errors of metabolism.</p>