Chronic Kidney Disease (CKD) has a strong association with chronic periodontitis, an oral disease causing tooth loss linked to inflammation and malnutrition. While periodontitis affects 12.7% of the general population, its prevalence can rise to 39% in certain racial groups, and a dose-response relationship exists with CKD. End Stage Renal Disease (ESRD) patients show a prevalence of periodontitis ranging from 29% to 85.6%. Uremia, immunosuppression, and vitamin D deficiency are suggested factors in the etiology of periodontitis in CKD patients, with uremic toxins potentially altering the oral ecosystem. Periodontitis involves bacterial biofilm and Gram-negative anaerobes as primary etiological factors. The main treatment goal is to reduce periodontal pathogens and control inflammation, with non-surgical periodontal therapy (NSPT) being the standard. Although various adjuncts like antibiotics and antiseptics are suggested, recent guidelines only recommend certain locally administered agents and systemic antibiotics for specific groups due to increasing bacterial resistance. Alternative treatments like honey have gained interest, particularly Manuka honey, known for its antibacterial properties against antibiotic-resistant bacteria. This honey's effectiveness is due to its high sugar concentration, low pH, and formation of hydrogen peroxide. Manuka honey's unique component, methylglyoxal (MGO), is a potent bactericide, virucide, and fungicide, linked to its Non-Peroxide Activity (NPA) and Unique Manuka Factor (UMF) rating. MGO also has immunomodulatory effects beneficial for wound healing and tissue regeneration. Previous studies show Manuka honey as a promising adjunct in NSPT, improving outcomes significantly without adverse effects. Ongoing research aims to evaluate its effects in ESRD patients on hemodialysis, focusing on clinical attachment levels, other periodontal parameters, and FGF 21 levels in gingival crevicular fluid.