Porphyromonas gingivalis (P.g) is a gram-negative bacterium found in the human oral cavity and is a recognized pathogenic bacterium associated with chronic periodontitis and systemic diseases, including chronic kidney disease (CKD), but the roles and molecular mechanism of P.g in CKD pathogenesis are unclear. In this study, an animal model of oral P.g administration and glomerular mesangial cells (GMCs) cocultured with M1-polarized macrophages and P.g supernatant were constructed. We found that oral P.g administration induced CKD in mice. P.g supernatant induced m! macrophage polarization and inflammatory factor upregulation, which triggered the activation of the NF‑κB/NLRP3 pathway and ferroptosis in GMCs. By inhibiting the NF‑κB/NLRP3 pathway and ferroptosis in GMCs, cell viability and the inflammatory response were partially alleviated in vitro. In conclusion, we demonstrated that P.g induced CKD in mice by triggering crosstalk between the NF‑κB/NLRP3 pathway and ferroptosis in GMCs. Overall, our study suggests that periodontitis can promote the pathogenesis of CKD in mice, which provides evidence of the importance of periodontitis therapy in the prevention and treatment of CKD.