Objectives: Primary: To determine the efficacy of periodontal treatment on mental health outcomes in patients with major depression and periodontitis. Secondary: To identify the effect of periodontal treatment on oral, periodontal, and fecal metagenomic microbiomes, and on systemic levels of inflammation (bacterial, viral, and fungal) and their impact on mental health outcomes. Material and method: A 6-month pilot randomized controlled clinical trial is designed. The study will be conducted in patients with moderate or severe DM (Patient Health Questionnaire-9 \[PHQ-9\] index of 9 or higher) and stage III-IV periodontitis who will be assigned to two different interventions: * Test group: standard periodontal treatment consisting of two sessions of supragingival and subgingival debridement (steps 1 and 2) under local anesthesia. * Control group: periodontal treatment consisting of two sessions of supragingival debridement (step 1) under local anesthesia. The study will consist of 6 visits: * Screening visit (v0) * Baseline visit (v1): * In the mental health center: patients will receive a structured clinical interview for the DSM-IV (SCID) and the patient will fill out a series of specific scales on a study-specific electronic device \[Beck Depression Inventory (BDI); UCLA Loneliness Scale, Center for Epidemiologic Studies Depression scale \[CES-D\]; Childhood Trauma Questionnaire short form (CTQ-SF); The World Health Organization Quality of Life questionnaire (WHOQOL); Hamilton scale (HAM-D17); Global Assessment of Functioning (GAF) Scale\]. * At the UCM School of Dentistry: patients will receive a complete periodontal examination (clinical and radiographic). A subgingival microbiological sample, a saliva sample and a blood sample will also be taken. * At the participant's home: the stool samples will be deposited by the participants at home in the specific collection vial. * Intervention visits (v2-3): Two periodontal treatment sessions (test or control) will be carried out one week apart. * Re-evaluation visit (v4): Six weeks after treatment, all periodontal clinical variables will be recorded. * Follow-up visits at 3 and 6 months: after periodontal treatment, all the variables recorded at the baseline visit will be taken Statistical analysis: Periodontal treatment (test/control) will be considered as the independent variable and the Hamilton scale (HAM-D17) will be considered the primary response variable. The rest of the variables will be considered as secondary variables. A crude bivariate analysis of comparison of means or proportions will be carried out depending on the nature of the variable. In addition, crude and adjusted regression models will be performed.