Pathogenic bacteria are attracted toward mucosa, as it is their way of entry into the body. However, we know surprisingly little about the phage-bacterium interactions in the mucosal environment. Here, we explored the effect of the mucosal environment on growth characteristics and phage-bacterium interactions in Streptococcus mutans , a causative agent of dental caries. We found that although mucin supplementation increased bacterial growth and survival, it decreased S. mutans biofilm formation. More importantly, the presence of mucin had a significant effect on S. mutans phage susceptibility. In two experiments done in Brain Heart Infusion Broth, phage M102 replication was detected only with 0.2% mucin supplementation. In 0.1 × Tryptic Soy Broth, 0.5% mucin supplementation led to a 4-log increase in phage titers compared with the control. These results suggest that the mucosal environment can have a major role in the growth, phage sensitivity, and phage resistance of S. mutans , and underline the importance of understanding the effect of mucosal environment on phage-bacterium interactions.