Gastrointestinal neuroendocrine tumors (GI NETs) remain diagnostically challenging due to limitations of current methods. This study pioneers the application of Fourier-transform infrared (FTIR) spectroscopy for GI NET detection through plasma lipid profiling. Analyzing 22 patients and 8 controls, we identified specific biomarker ratios (I3015/I2929 and I3015/I1650) reflecting tumor-associated oxidative stress and membrane alterations. Multivariate analysis revealed excellent diagnostic accuracy (94–96.1% sensitivity, 100% specificity) superior to conventional biomarkers, with PCA showing clear group separation (96.5% variance). The FTIR approach demonstrated significant advantages: rapid analysis (< 5 min), minimal sample requirements (4 μL), and low cost, addressing critical clinical needs. Spectral changes correlated with known lipid metabolism dysregulation in NETs, particularly increased unsaturated fatty acids (3015 cm−1) and altered acyl chain packing (2929 cm−1). These findings establish FTIR as a practical, label-free alternative to invasive diagnostics, with potential for both early detection and treatment monitoring. The identified lipid signatures not only provide robust diagnostic markers but also suggest new therapeutic targets for NET management. This cost-effective technology could transform clinical practice by enabling routine screening and personalized treatment strategies. Future studies should validate these results in larger cohorts and explore correlations with tumor grade and treatment response.