Surface Pre-Reacted Glass-ionomer (S-PRG) filler, which releases strontium (Sr2+), borate (BO33-), fluoride (F-), sodium (Na+), silicate (SiO32-), and aluminum (Al3+) ions at high concentrations, is a unique glass filler that are utilized in dentistry. Because of its multiple-ion releasing characteristics, S-PRG filler exhibits several bioactivities such as tooth strengthening, acid neutralization, promotion of mineralization, inhibition of bacteria and fungi, inhibition of matrix metalloproteinases, and enhancement of cell activity. Therefore, S-PRG filler per se and S-PRG filler-containing materials have the potential to be beneficial for various dental treatments and care. Those include restorative treatment, caries prevention/management, vital pulp therapy, endodontic treatment, prevention/treatment of periodontal disease, prevention of denture stomatitis, and perforation repair/root end filling. This review summarizes bioactive functions exhibited by S-PRG filler and its possible contribution to oral health.