Background: Periodontitis is a chronic infectious disease characterized by gingival inflammation and progressive destruction of alveolar bone. The interaction of periodontal plaque microorganisms and host immune response affects the process and progression of periodontitis. However, the specific mechanisms and biomarkers involved in periodontitis remain to be further studied. Methods: In the present research, we explored the expression profile data of differentially expressed lncRNAs and immune-related mRNAs and constructed the competing endogenous RNAs (ceRNA) network. The CIBERSORT analysis was used to infer the composition of 22 immune cells in periodontitis. The genes in ceRNA network were further screened by weighted gene co-expression network analysis (WGCNA), transcriptomic sequencing and PCR. Results: Our results indicated that a total of 1 lncRNA (KIAA0125), 3 miRNAs (miR-449c-5p, miR-125a-5p and miR-125b-5p) and 2 mRNAs (CYP24A1, BTG2) were involved in establishing the ceRNA network for periodontitis. The expression of KIAA0125 was highly correlated with plasma cells and B cells markers. The WGCNA and transcriptomic sequencing screened out the key gene as the vitamin D metabolic enzyme CYP24A1. The experimental results showed both KIAA0125 and CYP24A1 were highly expressed in the periodontitis gingival tissues. In vitro experiments, the expression of KIAA0125 in human periodontal ligament cells (hPDLCs) were increased after the treatment of lipopolysaccharide and 1,25-dihydroxyvitamin D3 (1,25D) (P < 0.05). In addition, we found that 1,25D could alleviate the inflammation of LPS-induced hPDLCs, while the increased expression of KIAA0125 and CYP24A1 would antagonize the anti-inflammatory effect. Conclusion: In conclusion, immune-related lncRNA KIAA0125 and vitamin D metabolism related gene CYP24A1 can be used as potential diagnostic indicators of periodontitis.