Introduction Chronic kidney disease (CKD) is known to cause an increase in fibroblast growth factor 23 (FGF23). Periodontitis, a condition recognized as a risk factor for CKD, is also potentially associated with the increment of FGF23. This study aims to compare FGF23 levels in CKD patients with and without periodontitis and non-CKD patients with and without periodontitis. Correlation with serum phosphate, calcium, and intact parathyroid hormone (iPTH) was assessed. Additionally, associations between FGF23, calcium, phosphate, iPTH, creatinine, urea, plaque score, and bleeding score with periodontitis in CKD patients were determined. Method A total of 124 participants were categorized into four groups: CKD patients with periodontitis (n=31), CKD patients without periodontitis (n=32), periodontitis patients without CKD (n=32), and healthy population (n=29). The selected CKD patients include those from stages 3 and 4 (predialysis) patients. Serum levels of FGF23, calcium, phosphate, iPTH, creatinine, and urea were analyzed. Oral examinations were conducted to determine the presence and absence of periodontitis and assess plaque and bleeding scores. Result A significantly higher level of FGF23 was found in CKD compared to non-CKD groups; however, no difference was observed with the presence of periodontitis in both CKD and non-CKD. There was no significant correlation found between FGF23 and serum calcium, phosphate, or iPTH concerning periodontal status. Apart from the bleeding score, there was no association between FGF23, calcium, phosphate, iPTH, creatinine, urea, and plaque score with the presence of periodontitis in CKD patients. Conclusion The presence of periodontitis was not associated with higher FGF23 levels in CKD patients. Changes in FGF23, calcium, phosphate, iPTH, creatinine, urea, and plaque score could not be attributed to the presence of periodontitis in CKD patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Human Research Committee of Universiti Sains Malaysia (USM) issued approval USM/JEPeM/22060382. The study protocol has been reviewed and granted approval for implementation. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This study was funded by the Ministry of Higher Education Malaysia under the Fundamental Research Grant Scheme (FRGS), grant number FRGS/1/2023/SKK11/USM/02/3. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Wan Abdul Azim et al.)