Background <p>Periodontal diseases have been reported to be associated with chronic kidney disease (CKD) progression. Thus, this study aimed to evaluate non-surgical periodontal therapy (NSPT) in patients with CKD disease progression by monitoring oral parameters, pathogen levels, cytokine profiles, and kidney function.</p> Methods <p>Forty-five participants (age 60.0 ± 8.5 years) were examined at baseline and at 3 months after NSPT for oral parameters, oral pathogens (<i>Porphyromonas gingivalis</i>, <i>Fusobacterium nucleatum</i>, <i>Aggregatibacter actinomycetemcomitans</i>, <i>Candida albicans</i>), cytokines (IL-6, IL-8, TNF-α, IL-10), and kidney functions (serum creatinine, eGFR, urine protein-creatinine ratio).</p> Results <p>At baseline, the CKD patients were diagnosed with stage II–IV periodontitis and exhibited measurable periodontal pathogen levels (<i>P. gingivalis</i>, 1.2 log CFU/mL; <i>F. nucleatum</i>, 4.4 log CFU/mL; <i>A. actinomycetemcomitans</i>, 0.3 log CFU/mL; and <i>C. albicans</i>, 4.1 log CFU/mL). Concurrently, pro-inflammatory cytokine concentrations were recorded at 0.2–4.4 pg/mL for IL-6, 1.9–25.5 pg/mL for IL-8, and 0.0–26.1 pg/mL for TNF-α. Conversely, IL-10 levels ranged from 0.0 to 13.2 pg/mL. After 3 months of NSPT, the levels of pathogens (1.1–10.9 fold) and cytokines (1.2–2.6 fold) were significantly reduced, while IL-10 levels significantly increased (0.7–1.9 fold). The number of patients showing improvement for serum creatinine and urine protein-creatinine ratio in CKD patients was 59.1–71.4% and 60.9–90.0%, respectively.</p> Conclusion <p>Our findings suggest that NSPT may benefit CKD patients by reducing oral pathogens and inflammation while increasing IL-10. There was evidence of a possible trend towards enhanced kidney function in CKD patients treated with NSPT.</p> Trial registration <p>The study was registered in the Thai Clinical Trials Registry (TCTR20240516002; registered date 16 May 2024), Thailand.</p>