Abstarct: Background and Objectives: Chronic kidney disease (CKD) is a progressive and irreversible condition affecting over 10% of the global population, often leading to various complications, including cardiovascular diseases. One significant complication is early arterial stiffness, which arises from oxidative stress and chronic vascular inflammation, contributing to the rapid deterioration of left ventricular function and altered tissue perfusion. Regular physical activity may mitigate inflammatory responses and enhance anti-inflammatory factors, potentially reducing arterial stiffness. This study aimed to evaluate the effect of resistance training on Klotho levels (an anti-inflammatory factor) and arterial stiffness (measured by the CAVI index) in CKD patients. Materials and Methods: This experimental clinical trial (IRCT20240107060639N1) involved CKD patients from Shahroud. A total of 27 participants were randomly assigned to either an exercise group (n=13; mean age: 48.3 ± 10.4 years; BMI: 24.6 ± 6.09 kg/m²) or a control group (n=14; mean age: 52.8 ± 13.98 years; BMI: 23.97 ± 4.09 kg/m²). The intervention comprised a resistance training program conducted three times per week for 12 weeks, with each session lasting 90 minutes and including nine exercises at 60% to 75% of one-repetition maximum (1RM). Blood samples were collected from participants in a fasting state 48 hours before and after the intervention for biochemical analysis. Klotho levels were measured via ELISA, while calcium, phosphorus, and creatinine levels were assessed using colorimetric enzymatic methods. Arterial stiffness was evaluated using the VASERA-VS-2000 system. Statistical analyses were performed using covariance analysis and paired t-tests with a significance level of p < 0.05. Results:Covariance analysis revealed significant improvements in Klotho levels, calcium levels, maximum upper and lower body strength, and central arterial stiffness (CAVI) in the exercise group compared to the control group (p < 0.05). Although covariance analysis did not show significant differences in glomerular filtration rate (GFR), systolic blood pressure, and body muscle mass between the groups (p > 0.05), paired t-tests indicated significant improvements in these parameters within the exercise group (p < 0.05). No significant differences were found between groups for phosphorus, calcium-phosphorus product, creatinine, body weight, body fat percentage, and body mass index (p>0.05). Conclusion: Resistance training significantly enhances Klotho levels, improves functional strength in both upper and lower body, increases active muscle mass, and reduces arterial stiffness in individuals with CKD. These effects may be mediated by changes in Klotho levels.