A previous study highlighted the superior shock absorption of silicone rubbers compared to other elastomers. We evaluated and compared the in vitro biocompatibility of silicone-based rubbers and propose them as an alternative to conventional products. We used the MTT colorimetric test to assess cell viability and flow cytometry to evaluate cell proliferation. Tests were conducted at 24 and 72 h. Changes in cell morphology were evaluated by scanning electron microscopy. Positive (polyurethane) and negative (polystyrene) toxicity controls were included. The number of viable cells was significantly higher on polystyrene than on polyurethane. A decrease in the total number of cells from 24 to 72 h compared to the negative control was correlated with a lower percentage of S-phase cells. The differences in cell viability noted between the samples and the polystyrene control mainly resulted from an initial lack of adhesion, which was confirmed by scanning electron microscopy. The biocompatibility of the three silicone rubbers was comparable to the best of the three products currently being used. These results, combined with those of the previous study, indicate that silicone rubber could be considered for the manufacture of mouth guards.