Purpose <p>We aimed to assess the associations between serum salusins levels and atherosclerosis, endothelial dysfunction and cardiac morphology in autosomal dominant polycystic kidney disease (ADPKD).</p> Methods <p>This study comprised 83 patients with ADPKD, and 53 healthy individuals. Salusin α and β levels were measured by ELISA. Echocardiography, flow-mediated vasodilatation, and carotid artery intima–media thickness measurements were conducted.</p> Results <p>Serum salusin α levels were significantly lower and the salusin β/α ratio was significantly higher in the patient group compared to Controls [2.64 (1.83–3.30) pg/mL vs. 3.20 (2.55–7.87) pg/mL, <i>P</i> = 0.002 and 2.81 (2.30–3.54) vs. 2.64 (2.02–3.18), <i>P</i> = 0.041, respectively]. Patients were further categorized into two groups: Group 1 (eGFR ≥ 60&#xa0;mL/min/1.73 m²) and Group 2 (eGFR = 59–15&#xa0;mL/min/1.73&#xa0;m²). The salusin α level was 2.31 (1.73–3.24) pg/mL in Group 2 and 2.72 (1.94–3.32) pg/mL in Group 1. In the correlation analysis performed in Group 2, there was a statistically significant negative correlation between salusin α and left ventricular mass (LVM) and LVM index (<i>P</i> = 0.019, <i>P</i> = 0.015, respectively), as well as a statistically significant positive correlation between salusin β/α ratio and LVM (<i>P</i> = 0.004) and LVM index (<i>P</i> = 0.025). In Group 1, a statistically significant positive correlation was detected between proteinuria and salusin β (<i>P</i> = 0.036).</p> Conclusion <p>In patients with ADPKD, salusin α was found to be significantly lower, while salusin β/α ratio was found to be significantly higher compared to healthy individuals. Low salusin α levels and high salusin β/α ratio were associated with LVM in advanced stages of ADPKD and salusin β was associated with proteinuria in early stage of ADPKD patients.</p>