Our earlier report has shown that salt substitutes (Obu-Otoyo) contain some toxic heavy metals. This study, therefore, investigated the effect of the dietary inclusion of salt substitutes (Obu-Otoyo), namely, salt “A” and “B”, on biomarkers of oxidative stress and renal function in rats. Salt “A”, which has a gray color, is the product of a process in which ash is produced by burning palm kernel shaft soaked in water overnight and extracting the residue to produce the salt substitute while Salt “B”, which has a white color, is a rock salt mined from a local site at Ilobu town, Osun-State, Nigeria. Salt substitutes were fed to normal rats as dietary inclusion at 0.5% and 1.0% for 21 days. The dietary inclusion of the salt substitutes caused a significant (p<0.05) increase in plasma activities of creatinine, urea, uric acid, and blood urea nitrogen compared with the control. Meanwhile, the dietary inclusion of the salt substitutes caused a significant (p<0.05) decrease in renal superoxide dismutase, catalase, reduced glutathione level, glutathione-S-transferase, and glutathione peroxidase activities with a concomitant increase in the malondialdehyde level compared with the control. Furthermore, there was a significant (p<0.05) increase in the concentrations of heavy metals, such as Pb, Co, Cu, Fe, Zn and Cr, in kidney of rats fed with the salt substitute Obu-Otoyo. Therefore, this finding indicates that Obu-Otoyo induces nephrotoxicity in rats. The nephrotoxicity of Obu-Otoyo could be attributed to the induction of oxidative stress as a result of the presence of some heavy metals, suggesting possible health hazards in subjects who consume it.