Periodontitis is an irreversible oral disease causing the destruction of tooth-supporting tissues. In addition to scaling and root planing (SRP) procedures, patients should achieve a correct domiciliary oral hygiene in order to maintain a healthy status. The aim of the present study was to evaluate the efficacy of different toothpastes in reducing gingival bleeding in periodontal patients. In addition to a professional treatment of SRP, 80 patients were randomly divided into four groups according to the toothpaste assigned for the daily domiciliary use using an electric toothbrush: Group 1 (Biorepair Gum Protection), Group 2 (Biorepair Plus Parodontgel), Group 3 (Biorepair Peribioma PRO), and Group 4 (Meridol Gum Protection) (control group). After baseline (T0), patients were visited after 15 days (T1), 3 months (T2), and 6 months (T3). At each appointment, the following periodontal indexes were assessed: bleeding on probing (BoP), full-mouth bleeding score (FMBS), and modified sulcus bleeding index (mSBI). All the experimental toothpastes caused an immediate significant modification of the three clinical indexes measured, except for the control product. Biorepair Peribioma PRO, with its paraprobiotic content, was also the only toothpaste causing a prolonged effect, reducing BoP even at T3. Accordingly, both hyaluronic acid and lactoferrin appear as reliable supports for the domiciliary management of periodontal disease. In spite of this, paraprobiotics are likely to show the most important benefit thanks to their immunomodulating mechanism of action.