Purpose <p>Henna artists are frequently exposed to para-phenylenediamine (PPD), a common hair dye component, raising concerns about its nephrotoxic effects. This study investigates the association between long-term PPD exposure and chronic kidney disease (CKD) among henna artists in Sudan.</p> Methods <p>A cross-sectional study included 138 female henna artists with over 10&#xa0;years of professional exposure. Clinical assessments, laboratory tests, and kidney biopsies in selected cases were conducted. Data were analyzed using SPSS to compare female artists with and without CKD.</p> Results <p>The mean age of participants was 36.4 ± 8.1&#xa0;years, with 15.8 ± 6.3&#xa0;years in the profession. CKD was diagnosed in 27 (19.6%) participants, with persistent hematuria in 19 (70.4%), combined hematuria and proteinuria in 8 (29.6%), and elevated creatinine in 5 (18.5%). Kidney biopsies from 23 participants revealed the presence of chronic tubulointerstitial nephritis in 14 (60.9%), focal segmental glomerulosclerosis in 6 (26.1%), and membranoproliferative glomerulonephritis in 3 (13%) participants. CKD was more common among the unmarried (<i>P</i> = 0.033), those with lower education (<i>P</i> = 0.019), those who worked longer hours (<i>P</i> = 0.015), use high-concentration PPD formulations (<i>P</i> &lt; 0.0001), and work in family parlors rather than professional salons (<i>P</i> = 0.023). CKD was also linked to PPD-induced skin reactions (<i>P</i> &lt; 0.05) and the presence of normochromic normocytic anemia (<i>P</i> = 0.024).</p> Conclusion <p>This study suggests an association between prolonged PPD exposure and CKD risk among female henna artists. These findings underscore the need for greater awareness and further investigation into PPD’s nephrotoxic effects.</p>