Hydroxyapatite (HA) forms an essential constituent of human teeth and bone. Its distinctive characteristic features, such as bioactivity and osteoconductivity, make it an ideal candidate to be used as an implant coating in restorative dentistry and maxillofacial surgery for bone regeneration. However, low fracture toughness and brittleness are a few of the inherent features of HA, which limit its application in load-bearing areas. The potential of HA to engage its lattice structure with either partial or complete substitution with external ions has become an increasing area of research as this phenomenon has the potential to enhance the biological and functional properties of the material. Consequently, this review aimed to highlight the role of various substituted ions in dental applications. Data indicate that the newly formed HA-substituted biomaterials demonstrate enhanced remineralization and antimicrobial activity along with improved hardness. Ion-substituted HA offers a promising strategy for future clinical research as these materials may be incorporated into various dental products for therapeutic treatments.