Hydroxyapatite (HA) is the main inorganic constituent of human hard tissue. It can effectively accelerate the repair process of hard tissue defects due to its high bioactivity and biocompatibility. Ion doping is an effective approach to enhance the bioactivity of HA materials. On this basis, dual-ion substitution can make HA materials have a higher simulation to nature bone in composition and some functional features (i.e., antitumor ability, antibacterial activity, pro-angiogenetic capacity, immunoregulatory and medical imaging capability). Dual-ion substitution greatly extends the applications of HA materials in bone tissue engineering. This review summarized the synthesis methods and their principles of dual-ion substituted HA (DIHA) materials, represented the applications of DIHA materials in hard tissue engineering, and finally proposed the future development direction of DIHA materials.