Aim: Periodontitis has been associated with other systemic diseases with underlying inflammation responsible for the shared link. This study evaluated longitudinal variation in peripheral T helper cells in periodontitis patients undergoing management over 1 year. Materials and methods: Periodontal parameters and peripheral blood mononuclear cells (PBMCs) were collected from 54 periodontitis patients at baseline, and 3-, 6-and 12-months post-treatment and 40 healthy controls. IFN-γ + , IL-4 + , IL-17 + and Foxp3 + and their double-positive expression were identified in CD4 + and TCRαβ + cells using flow cytometry. PBMCs were incubated with P. gingivalis, and IFN-γ, IL-4, IL-17 and IL-10 in cell supernatant were measured by ELISA. Cells and cytokines were also assessed based on clinical response to treatment where good (<10% of sites), moderate (10-20%) and poor (>20%) treatment outcome (TxO) groups had probing depths of ≥5 mm at study conclusion. Results: IFN-γ + cells were lower at baseline, and 3-and 6-months compared to health, whereas Foxp3 + cells were increased at 12-months compared to all preceding timepoints and health. The good TxO group showed treatment-related variation in IFN-γ + and Foxp3 + cells, whereas the poor TxO group did not. IFN-γ and IL-17 cytokine expression in cell supernatants was significantly lower at baseline compared to health, and IFN-γ and IL-10 showed treatment-related decrease. Conclusion: This study suggests that IFN-γ + and Foxp3 + cells may have a role in the systemic compartment in periodontitis. Periodontal management has local and systemic effects, and thus, assessment and management of periodontitis should form an integral part of overall systemic health.