Background <p>Residual root canal microbiota in the inaccessible areas of the root canal despite cleaning and shaping and the adverse effects of the various root canal irrigants on dentin mineral content pose a major challenge to successful root canal therapy. The aim of this study was to develop therapeutic and bioactive resin-based root canal sealer (RCS) with good wetting ability.</p> Methods <p>Silver polydopamine-modified hydroxyapatite (HA-PDA-Ag-PDA) fillers were synthesized. Hydroxyapatite particles were analyzed using X-ray diffraction (XRD), while the final prepared fillers were characterized by Fourier transform infrared (FT-IR) spectroscopy and transmission electron microscopy (TEM). The resin-based RCS (Adseal^®) served as the control group (G0). Two concentrations of HA-PDA-Ag-PDA fillers (1 wt% and 2 wt%) were incorporated into the tested RCS (G1 and G2), respectively. The antibacterial properties, mineralization, and wettability of unmodified RCS (G0) and modified RCS (G1 and G2) were evaluated. The data were analyzed by one-way ANOVA, followed by a post hoc test for pairwise comparisons.</p> Results <p>XRD, FT-IR, TEM characterizations confirmed the successful synthesis of the HA-PDA-Ag-PDA fillers. Modified RCS showed strong bacterial inhibition effect against E. faecalis with insignificant difference between G1 and G2. Modified RCS (G1 and G2) also showed good mineralization potential and improvement in wettability of dentin surface.</p> Conclusions <p>HA-PDA-Ag-PDA fillers significantly improved the antibacterial, mineralization properties as well as the wetting ability of resin-based RCS.</p>