Type 2 diabetes mellitus (T2DM) is a complex clinical syndrome characterized by insulin resistance and associated with abnormal amino acid metabolism. Tryptophan is an aromatic dietary amino acid that affects T2DM by regulating glycolipid metabolism and insulin resistance. When tryptophan reaches the intestine, it is converted by gut microbiota and tryptophanase into indole derivatives such as indoleacetic acid, indolepropionic acid, and indolealdehyde. These indole derivatives may enhance insulin sensitivity, stimulate insulin secretion, and exert functions such as lowering blood glucose, regulating hepatic oxidative stress, reducing intestinal inflammation, and improving islet cell morphology by acting on the aryl hydrocarbon receptor (AHR) or Pregnane X receptor (PXR). In summary, this review aims to examine the interactions between tryptophan indole derivatives and T2DM thoroughly, elucidate potential therapeutic approaches, and pinpoint areas for further research.