Objectives <p>Caries is a significant public health challenge. Herein, novel tooth-targeting antimicrobial peptides (HABPs@AMPs) were developed by combining the antimicrobial peptide DJK-5 with hydroxyapatite (HA) binding peptides, providing a potential new strategy for caries management.</p> Materials and methods <p>The minimal inhibitory concentration (MIC₁₀₀) and minimal biofilm inhibitory concentration (MBIC₁₀₀) values of HABPs@AMPs were determined via micro-broth dilution and crystal violet staining. The affinities of the peptides for HA were measured by mass depletion, and the abilities of peptides to inhibit <i>Streptococcus mutans (S. mutans)</i> biofilm formation and kill 3-day-old <i>S. mutans</i> biofilms were evaluated in HA disk and tooth slice biofilm models through confocal laser scanning microscopy. Biocompatibility with human gingival fibroblasts was evaluated via CCK8 assays.</p> Results <p>The best performing peptides, DJK-5@SVA and SVA@DJK-5 exhibited MIC₁₀₀ and MBIC₁₀₀ values of 31.25&#xa0;µg/mL, similar to DJK-5. DJK-5@linker2@YSL had the highest affinity for HA, followed by YSL@DJK-5, DJK-5@linker1@YSL, and DJK-5@SVA. Moreover, the biofilms on HABPs@DJK-5 coated surfaces had more dead bacteria by volume than those in the DJK-5 and SVA groups (<i>p</i> &lt; 0.05). DJK-5@SVA outperformed SVA@DJK-5 and DJK-5 in killing 3-day-old <i>S. mutans</i> biofilms (<i>p</i> &lt; 0.05). With the exception of established biofilms on tooth slices, DJK-5@SVA exhibited greater killing efficiency in the bottom half of the biofilms than in the top half. The CCK-8 assay results confirmed peptides’ biocompatibility.</p> Conclusions <p>DJK-5@SVA with good affinity for HA, has excellent biocompatibility and efficacy against <i>S. mutans</i> biofilms.</p> Clinical Relevance <p>HABPs@AMPs with effective inhibitory effects on the growth of <i>S. mutans</i> and biofilm formation, contributing to intraoral targeted application AMPs and providing a new strategy for caries management.</p>