Gamma-aminobutyric acid (GABA) plays a crucial role in signal transduction and can function as a neurotransmitter. Although many studies have been conducted on GABA in brain biology, the cellular function and physiological relevance of GABA in other metabolic organs remain unclear. Here, we will discuss recent advances in understanding GABA metabolism with a focus on its biosynthesis and cellular functions in other organs. The mechanisms of GABA in liver biology and disease have revealed new ways to link the biosynthesis of GABA to its cellular function. By reviewing what is known about the distinct effects of GABA and GABA-mediated metabolites in physiological pathways, we provide a framework for understanding newly identified targets regulating the damage response, with implications for ameliorating metabolic diseases. With this review, we suggest that further research is necessary to develop GABA's beneficial and toxic effects on metabolic disease progression.