Dentin and enamel loss related to trauma or especially caries is one of the most common pathological issues in dentistry that requires restoration of the teeth by using materials with appropriate properties. The composite resins represent dental materials with significant importance in today’s dentistry, presenting important qualities, including their mechanical behavior and excellent aesthetics. This paper focuses on the saliva interactions with these materials and on their biocompatibility, which is continuously improved in the new generations of resin-based composites. Starting from the elements involved on the molecular landscape of the dental caries process, the paper presents certain strategies for obtaining more advanced new dental composite resins, as follows: suppression of oral biofilm acids formation, promotion of remineralization process, counteraction of the proteolytic attack, and avoidance of cytotoxic effects; the relation between dental composite resins and salivary oxidative stress biomarkers is also presented in this context.