Glucose transporter 3 (GLUT3), a high-affinity glucose transporter, is markedly overexpressed in colorectal cancer (CRC) and plays a pivotal role in sustaining tumor metabolism and proliferation. However, selective inhibition of GLUT3 remains a pharmacological challenge due to structural redundancy among GLUT isoforms. Here, we report SGT-24093, a novel small-molecule hit compound that selectively targets GLUT3 and impairs glucose metabolism in CRC cells. From a high-throughput screen of ~100 compounds, 22 hits demonstrated significant cytotoxicity in HCT116 cells. Among these, SGT-24093 exhibited the most potent suppression of glucose uptake and ATP production, accompanied by marked downregulation of GLUT3 at both transcriptional and protein levels. SGT-24093 shows high isoform selectivity, sparing GLUT1 and GLUT4, thereby addressing a key limitation of current GLUT inhibitors. It induces dose-dependent inhibition of CRC cell proliferation (IC₅₀ = 10.49 µM) while exhibiting minimal cytotoxicity in normal colon epithelial cells (IEC6), indicating a favorable therapeutic index. Comparative analyses further demonstrate the superior metabolic and anti-proliferative activity of SGT-24093 over its structural analogue, SGT-240101. Mechanistically, SGT-24093 disrupts GLUT3-mediated metabolic pathways, ultimately leading to selective CRC cell death. Collectively, these findings position SGT-24093 as a promising GLUT3-targeting hit compound, offering a novel strategy to exploit metabolic vulnerabilities in CRC and potentially other GLUT3-driven malignancies.