Aim To determine the potential anti-inflammatory effect of a multimodal periodic fasting programme on surrogate parameters of periodontal inflammation in hospitalized patients diagnosed for metabolic syndrome (MetS). Material and methods A total of 47 patients were recruited and hospitalized in an integrative ward for an intensified two-week multimodal fasting, diet and lifestyle programme. Patients were periodontally examined at baseline (t1), after the 2-week fasting protocol (t2) and, subsequently, 4 months after fasting (t3). The following parameters were determined: periodontal screening index (PSI), bleeding on probing (BOP), gingival crevicular fluid volume (GCF), plaque index (PI), C-reactive protein (CRP), blood pressure (BP), waist circumference (WC), fasting glucose (FGLU), triglycerides (TRG), high-density lipoprotein (HDL) and HbA1c. Results A total of 28 female and 8 male patients fulfilled the defined criteria for MetS and were analysed separately by gender. At t2, BOP and GCF were reduced when compared to t1 (median: t2 = 39; t1 = 33.1%; p p = .02, respectively). BOP reduction correlated to FGLU (R = .37, p = .049) and weight reduction (R = .4, p = .04). Conclusion This study showed for the first time that clinically supervised periodic fasting in female patients with MetS may facilitate the reduction of periodontal inflammation.