Purpose To reduce the toxicity and achieve a sustainable and controllable release of cisplatin (CDDP). Methods CDDP was loaded onto Fe5 (Fe3+ doped hydroxyapatite at atomic ratio of Feadded/Caadded = 5%) nanoparticles through surface adsorption. Subsequently, CDDP-loaded Fe5 nanoparticles (CDDP-Fe5) and/or CDDP were encapsulated into poly(lactide-co-glycolide) (PLGA) microspheres using oil-in-water single emulsion. Drug release profiles and degradation behaviors were monitored. Results CDDP-Fe5 demonstrated a high initial burst (42% on day 1) and short release time (25 days) as CDDP was directly released from Fe5 nanoparticles. CDDP-Fe5 encapsulated within the PLGA microspheres revealed a lower initial burst (23% on day 1) and longer release time (55 days) than CDDP-Fe5. Compared with PLGA microspheres containing only CDDP, which showed typical biphasic release manner, microspheres with CDDP-Fe5 and CDDP demonstrated a nearly linear release after the initial burst. Fe5 and CDDP delayed microsphere degradation. All samples became porous, disintegrated, fused, and formed pellets at the end of the study. Conclusion Fe5/PLGA composite microspheres showed favorable CDDP release behavior compared to microspheres composed of polymer alone, suggesting its potential as a new CDDP formulation.