Introduction: The number of Firmicutes and Bacteroidetes in the intestine is influenced by diet. Gut microbiota and fibroblast growth factor 21 (FGF21) form a liver-gut axis that mediates the body’s response to protein restriction. Bambara groundnut (Vigna subterranea), which contains high levels of amino acids, has the potential to be a source of protein. This study aimed to determine the effect of Bambara groundnut on the number of Firmicutes and Bacteroidetes, FGF21 gene expression, and liver histopathology in mice fed with a low-protein diet. Methods: A total of 25 mice were divided into five groups: normal protein diet (N), lowprotein diet (LP), and low-protein diet with supplementation of 100 g (LPLB), 200 g (LPMB), and 300 g (LPHB) of Bambara groundnut, respectively. After 2 months of intervention, mice were sacrificed, the number of Firmicutes and Bacteroidetes in the intestines and faeces, as well as FGF21 gene expression were analysed, while liver histopathology was visualised. Results: Results showed that Bambara groundnut supplementation increased the growth of Firmicutes and Bacteroidetes, decreased FGF21 gene expression, and reduced liver inflammation caused by a lowprotein diet. Conclusion: Bambara groundnut supplementation has the potential to increase the amount of Firmicutes and Bacteroidetes, decrease the expression of adaptive stress gene FGF21, and improve the degree of liver inflammation in a lowprotein diet.