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Purpose: Acromegaly is a rare disease caused by chronic hypersecretion of growth hormone, which leads to multiple comorbidities and reduced life expectancy. The objective of this study was to characterize the serum metabolic profiles of acromegaly patients and identify metabolic biomarkers using metabolomics. Methods: Twenty-nine active acromegaly patients and age- and sex-matched normal controls were recruited. Serum samples were collected, and serum metabolites were analyzed using gas chromatography–mass spectrometry coupled with a series of multivariate statistical analyses. Results: The orthogonal projections to latent structures-discriminate analysis (OPLS-DA) model identified and validated significant metabolic differences between individuals with acromegaly and normal controls (R2Y = 0.908 and Q2Y = 0.601). Compared with normal controls, acromegaly patients had elevated levels of 5-aminovaleric acid, glyceric acid, l-dithiothreitol, dihydrocoumarin, N-acetyl-L-glutamic acid, gluconic acid, and monoolein (P < 0.05) and reduced serum levels of d-erythronolactone, taurine, carbamoyl-aspartic acid, and mucic acid (P < 0.01). Furthermore, glyceric acid and taurine possessed higher area under the receiver operating characteristic curve values (AUC values, 0.914 and 0.931, respectively), suggesting an excellent clinical ability to distinguish acromegaly patients from normal controls. Pathway analysis revealed that the pentose phosphate pathway and the taurine and hypotaurine metabolic pathway are significant pathways (P = 0.002 and 0.004, respectively). Conclusions: Metabolic activity is significantly altered in the serum of individuals with active acromegaly. Glyceric acid and taurine may be considered potential biomarkers for distinguishing acromegaly patients from normal controls. [ABSTRACT FROM AUTHOR]