Aim: To evaluate and correlate the salivary urea and creatinine levels to the serum levels in smokeless tobacco (SLT) chewers. Materials and methods: The present study included 60 subjects, 30 SLT chewers, and 30 controls aged between 20 years and 60 years. Serum and salivary urea and creatinine levels were estimated using Berthelot-urease method enzymatic colorimetric method and modified Jaffe's method, respectively. Results: The mean salivary urea, mean serum, and salivary creatinine levels were higher in SLT chewers (33.77 ± 15.04, 0.76 ± 0.17, and 0.17 ± 0.07 mg/dL, respectively) than controls (32.3 ± 14.73, 0.67 ± 0.15, and 0.13 ± 0.05 mg/dL, respectively). Although serum and salivary urea showed a strongly positive correlation (r = 0.654, p < 0.001**) among SLT chewers and controls, no correlation was noted for serum and salivary creatinine (r = 0.098, p = 0.606). Receiver operating curve (ROC) analysis revealed better sensitivity and specificity of serum and salivary creatinine than for urea among both SLT chewers and controls. Conclusion: Salivary urea, serum, and salivary creatinine levels were higher among SLT chewers than controls showing that SLT can be nephrotoxic. Clinical significance: Smokeless tobacco chewers can be assessed for early renal damage caused by the tobacco products using salivary parameters of urea and creatinine so that they can be counseled for the risk of renal diseases and referred appropriately.