Iron oxide magnetic nanoparticles have emerged as promising theranostic agents for cardiovascular diseases. Using a multiscale approach, we investigated the interaction of 26.5 nm diameter multicore magnetite nanoflowers, recognized for being excellent nanoheaters and contrast agents in nanomedicine, with human blood platelets. Using flow cytometry, we determined safe concentration levels of magnetite nanoflowers. Data indicated that platelets exhibit reversible activation at high magnetite nanoflowers concentrations. Magnetic resonance imaging revealed significant reductions in T1 and T2 relaxation times when platelets were combined with magnetite nanoflowers at high concentrations suggesting nanoparticle -platelets interaction. At the nanoscale, transmission and scanning electron microscopy confirmed morphological changes in platelets when exposed to high concentration of nanoparticles and their partial internalization in the platelets. Overall, the findings support the theranostic potential of magnetite nanoflowers in whole blood for thromboembolic disease management, with potential for future investigations over longer exposure.