Secondary caries is one of the leading causes of resin-based dental restoration failure. It is initiated at the interface of an existing restoration and the restored tooth surface. It is mainly caused by an imbalance between two processes of mineral loss (demineralization) and mineral gain (remineralization). A plethora of evidence has explored incorporating several bioactive compounds into resin-based materials to prevent bacterial biofilm attachment and the onset of the disease. In this review, the most recent advances in the design of remineralizing compounds and their functionalization to different resin-based materials’ formulations were overviewed. Inorganic compounds, such as nano-sized amorphous calcium phosphate (NACP), calcium fluoride (CaF2), bioactive glass (BAG), hydroxyapatite (HA), fluorapatite (FA), and boron nitride (BN), displayed promising results concerning remineralization, and direct and indirect impact on biofilm growth. The effects of these compounds varied based on these compounds’ structure, the incorporated amount or percentage, and the intended clinical application. The remineralizing effects were presented as direct effects, such as an increase in the mineral content of the dental tissue, or indirect effects, such as an increase in the pH around the material. In some of the reported investigations, inorganic remineralizing compounds were combined with other bioactive agents, such as quaternary ammonium compounds (QACs), to maximize the remineralization outcomes and the antibacterial action against the cariogenic biofilms. The reviewed literature was mainly based on laboratory studies, highlighting the need to shift more toward testing the performance of these remineralizing compounds in clinical settings.