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ABSTRACT This study investigates the morphological, thermal, mechanical, and bioactive properties of centrifugally spun fibrous composites made from poly(D,L‐lactide)/poly(3‐hydroxybutyrate) (PLA/PHB) blends with zinc oxide (ZnO) and hydroxyapatite (Hap) nanoparticles. A 75/25 PLA/PHB weight ratio was chosen to balance mechanical and thermal properties. The precursor solution viscosities ranged from 0.25 to 0.50 Pa s, increasing with nanoparticle incorporation probably due to polymer‐nanoparticle interactions. SEM revealed a uniform fibrous morphology, with diameters of 1.21 for PLA/PHB, 2.65 for PLA/ZnO/Hap, and 1.80 μm for PLA/PHB/ZnO/Hap. TGA showed two‐step degradation for PLA/PHB fibers, while PLA/PHB/ZnO/Hap degraded in a single step at 249°C, leaving a residue of 9.95%. DSC indicated partial miscibility, with cold crystallization at 85°C (enthalpy: 7.72 J/g), slightly modified by nanoparticle addition. PLA/PHB fibers achieved a Young's modulus of 24.96 ± 3.91 MPa, three times that of pure PLA, but adding ZnO and Hap reduced modulus and tensile strength to 6.03 and 0.29 MPa, retaining suitability for biomedical applications. PLA/PHB/ZnO/Hap fibers exhibited 90%Escherichia coligrowth inhibition and enhanced MC3T3‐E1 cell viability by 120% on day 7. These results highlight their potential for antimicrobial, biocompatible medical devices.