Background: The objective of this study was to evaluate the serum and salivary L-fucose in oral potentially malignant disorders (OPMDs) and oral cancer (OC) in order to investigate the possibility of using this as biomarker for early diagnosis. Materials and Methods: The study included 85 participants, who were grouped as control (30), OPMDs patients (25), and OC patients (30). Serum and unstimulated whole saliva were collected from participants of all groups and fucose estimation was done using spectrophotometry. The results were tabulated and analyzed statistically. Results: The mean serum L-fucose levels in normal, OPMDs, and OC group were 3.49, 19.18, and 35.75 mg/dl, respectively, while the levels of salivary L-fucose were 3.18, 7.02, and 11.66 mg/dl, respectively. A highly significant rise (P < 0.001) in serum and salivary L-fucose was observed in the study participants compared to control. Conclusions: The present study showed a significant and gradual increase in serum and salivary L-fucose from control to OPMDs to OC. From this study, we suggest that L-fucose can be used as a reliable biomarker and saliva can be used as a diagnostic fluid for screening and early detection of OC.