© 2022 Wiley Periodicals LLC.Simvastatin (SIM)-loaded and human decellularized adipose tissue (DAT)-coated porous hydroxyapatite (HAp) microspheres were developed for the first time to investigate their potential on bone regeneration. Microspheres were loaded with SIM and then coated with DAT for modifying SIM release and improving their biological response. HAp microspheres were prepared by water-in-oil emulsion method using camphene (C10H16) as porogen followed by camphene removal by freeze-drying and sintering at 1200°C for 3 h. Sintered HAp microspheres with an average particle size of ~400 µm were porous and spherical in shape. Microspheres were incubated with 1, 2.5, and 5 mg/ml SIM stock solutions for drug loading, and drug loading was determined as 7.5 ± 0.79, 20.41 ± 1.93, and 46.26 ± 0.29 µg SIM/mg microspheres, respectively. SIM loading increased with the increase of the initial SIM loading amount. Faster SIM release was observed in DAT-coated microspheres compared to bare counterparts. Higher SaoS-2 cell attachment and proliferation were observed on DAT-coated microspheres. Significantly higher alkaline phosphatase activity of SaoS-2 cells was observed on DAT-coated microspheres containing 0.01 mg/ml SIM than all other groups (p < 0.01). DAT-coated microspheres loaded with SIM at low doses hold promise for bone tissue engineering applications.