Introduction: Lead (Pb) occupational exposure in painters has been documented to be contacted via additives in paints due to its many important properties and vitamin C has been the most widely studied when it comes to Pb- induced oxidative stress. Aim: This study aimed at the use of freshly squeezed orange-juice due to its accessibility in investigating the modulating role of synthetic and natural vitamin-C on leaded paint-induced nephrotoxicity of automobile painters. Study Design and Methods: Sixty (60) male automobile painters were consecutively selected and divided equally into 2 groups. Vitamin-C and orange juice were administered daily to painters for 4 weeks at dosage levels of 200 and 184 mg/day respectively. Thirty (30) male non-painters constituted the control group. Orange juice vitamin-C content was assessed by titrimetric method and synthetic vitamin-C served as the standard drug. Renal biomarkers and reduced glutathione (GSH) were done by Colorimetry. Urine aminolevulinic acid (ALA) and Pb were assessed by ELISA technique and atomic absorption spectrophotometry respectively. Phytochemical screenings (quantitative/qualitative) and proximate analysis were done using standard methods. Data were analyzed using Pearson’s correlation coefficient and One-way Analysis of Variance (ANOVA) followed by Tukey’s post-hoc test for pairwise comparison. Statistical significance was p< 0.05. Results: Baseline results at 0-week of orange juice administered group showed a significantly (P<0.05) higher serum Pb, urea and creatinine compared to non- painters. Also, their urine baseline results at 0-week showed a significantly (P<0.05) higher levels of ALA and GSH compared to non-painters. Orange juice administration at 4 weeks showed significant (P<0.05) reductions in concentrations of lead, urea, and creatinine in serum, decreased concentrations of GSH and ALA in urine but increased urine Pb compared to baseline. However, compared with baseline, after 4 weeks of vitamin-C supplementation, serum Pb, urine GSH, and urine ALA were significantly (P<0.05) reduced and urine Pb significantly (P<0.05) increased. A positive correlation was observed at 2-weeks of taking orange- juice between serum lead and urine ALA (r= 0.703) and GSH (r= 0.913) but 4-week positive correlation between urea and urine GSH (r= 1.000). A negative correlation was observed at 2-week of taking vitamin-C between serum creatinine and urine lead (r= -0.857) while 4-week a negative correlation was observed between urine GSH and urine lead (r= -0.743). Presence of tannin, phenol, saponin, alkaloid, and flavonoid was detected in orange juice. Conclusion: Orange juice administration conferred significant amelioration to renal and lead toxicity biomarkers by 4 weeks. The presence of phytochemicals suggests why orange juice may be a viable alternative in amelioration of toxic effects of leaded paint among automobile painters.