As a multidimensional metabolic disorder, the disability and death rate of type 2 diabetes mellitus (T2DM) has increased over time. T2DM covers a wide range of pathological manifestations ranging from hyperglycemia to multi-organ failure, and it has the potential to evolve into acute complications, including ketosis and chronic complications such as peripheral neuropathy, retinopathy, and nephropathy. T2DM mainly occurs in microvascular and large vessels and thus it is restricted for the clinician to diagnose and prescribe. However, the pathological mechanism and clinical diagnosis are inadequate. High-throughput metabolomics, characterized by non-invasive diagnostic techniques to identify potential biomarkers and distinct stages of T2DM, has been increasingly recognized as a vigorous tool with latent capacity for clinical translation. The pathological stratification of T2DM can significantly reduce disability and mortality rates. By tracing the metabolome and associated pathways from impaired fasting blood glucose or impaired glucose tolerance to severe organ failure, the chief contributions of large, independent population-based cohorts are summarized herein. These results facilitate understanding the pathophysiology and mechanism and supports research in accurate diagnosis, risk prediction, curative effect, distinct stages, and prognosis judgment of T2DM.