We have previously reported that syringic acid (SA) extracted from D. aurantiacum var. denneanum (kerr) may be used to prevent diabetic cataract (DC). However, the underlying mechanisms through which SA prevents DC in human lens epithelial cells (HLECs) remained unclear. In the present study, we employed single-molecule optics technologies, including transmission electron microscopy (TEM), atomic force microscopy (AFM), laser scanning confocal microscopy (LSCM) and Raman spectroscopy, to monitor the effect of SA on HLECs biomechanics and organelle structure in real-time. TEM suggested that SA improved the ultrastructure of HLECs with regard to nuclear chromatin condensation and reducing mitochondrial swelling and degeneration, which may aid in the maintenance of HLECs integrity in the presence of glucose. AFM revealed a reduced surface roughness and stiffness following SA treatment, suggesting an improved viscoelasticity of HELCs. Raman spectrometry and LSCM further revealed that these changes were related to a modification of cell liquidity and cytoskeletal structure by SA. Taken together, these results provide insights into the effects of SA on the biomechanics of HLECs and further strengthen the evidence for its potential use as a novel therapeutic strategy for DC prevention.