Background: It is well-known that toothbrushing might be associated with the development of oral soft tissue lesions. There is currently a continuing increase in the demand for new safety and performing materials in daily homecare oral hygiene including soft and extra-soft toothbrush bristles that tend to be safer. The aim of this study was to compare the efficacy of plaque control and the potential effects on gingival health of two different toothbrush bristle models. Methods: In a three-month period, a total of forty subjects were evaluated for Oral Hygiene Index (OHI), Gingival Index (GI) and Plaque Index (PI) scores as well the Gingival Abrasion Assessment (GAA) between a toothbrush entirely made from a rubber-like material called thermoplastic elastomer (TPE) and a soft toothbrush (standard control with nylon bristles) in a clinical, single-blind, controlled, parallel-group trial. Results: The use of the TPE toothbrush allows a reduction in the PI, improves the OHI and modifies the GAA in the TPE group over a period of three months compared with a conventional soft bristle toothbrush applied for the same period, leading in this way evidence for a good influence of the TPE bristles on overall oral hygiene conditions. Conclusions: From the comparison between our data and the literature studies, we can state that the material and shape of the bristles of the toothbrush affect the home practice of oral hygiene. The TPE bristles reduce the presence of plaque formation and gingival bleeding, oral soft tissue injuries acquired during homecare oral hygiene.