OBJECTIVES: The aim of this study was to test the feasibility of a fasting mimicking diet on the systemic and periodontal response following non-surgical periodontal therapy. METHODS: Twenty patients with periodontitis were randomized to receive steps 1 and 2 of periodontal treatment alone (following their normal diet) or with an adjunctive 5-day course of fasting-mimicking diet (FMD). Blood and gingival crevicular fluid (GCF) samples were collected to study the levels of inflammatory biomarkers, along with clinical parameters and patients reported outcome measurements (PROMs). All patients were followed up at day-1, day-7 and 3 months post-treatment and food diaries were completed to assess their compliance. RESULTS: Nineteen patients completed the 3-months follow-up. Only minimal adverse events including nausea, fatigue, weakness and dizziness were reported in the test group, with no differences in PROMs between groups. Test patients exhibited a non-statistically significant 3-months serum hs-CRP reduction of 0.20 ± 0.30 mg/l compared with 0.11 ± 0.52 mg/l in controls (p=0.632) and a trend for lower GCF levels of MMP-8, IL-6 and IL-1B post-treatment compared with controls. CONCLUSIONS: This study suggests that one cycle of adjunctive FMD is feasible and may modulate the inflammatory response post-non-surgical periodontal therapy. Larger studies are needed to test this hypothesis. (clinicaltrials.gov ID: NCT05684627).