Background: The relation between diabetes mellitus and periodontitis has been discussed for years. Many adipokines were reported to play a major role in periodontal inflammation. Chemerin is one of these adipokines which is blamed to be involved in inflammatory conditions such as diabetes. Fibroblast growth factor 21 (FGF21) is another adipokine which is believed to induce regulation of glucose. The current study aimed to spot the light on the potential role of gingival crevicular fluid (GCF) level of FGF21 and chemerin as biomarkers of periodontal disease activity and an attempt to understand their role in the link between periodontitis and diabetes.  Methods: The study was conducted on 45 individuals, 15 diabetic patients with periodontitis, 15 periodontitis patients and 15 healthy controls. GCF samples were collected from all participants for assessment of chemerin and FGF 21. Samples were analysed using enzyme linked immunosorbent assay (ELISA). Results:  Periodontitis patients with diabetes had significant higher levels of chemerin and FGF21 than the periodontitis patients without diabetes followed by healthy controls. ROC analysis showed a 100% diagnostic accuracy for chemerin and FGF21. Conclusion: FGF21 and chemerin in GCF are valuable biomarkers of periodontal disease suggesting a role in the link between diabetes and periodontitis.