The chemical, physical and biological effects of chiral nanomaterials have inspired general interest and demonstrated important advantages in fundamental science. Here, chiral iron oxide supraparticles (Fe O SPs) modified by chiral penicillamine (Pen) molecules with g-factor of ≈2 × 10 at 415 nm are fabricated, and these SPs act as high-quality magnetic resonance imaging (MRI) contrast agents. Therein, the transverse relaxation efficiency and T -MRI results demonstrated chiral Fe O SPs have a r relaxivity of 157.39 ± 2.34 mM ·S for D-Fe O SPs and 136.21 ± 1.26 mM ·S for L-Fe O SPs due to enhanced electronic transition dipole moment for D-Fe O SPs compared with L-Fe O SPs. The in vivo MRI results show that D-Fe O SPs exhibit two-fold lower contrast ratio than L-Fe O SPs, which enhances targeted enrichment in tumor tissue, such as prostate cancer, melanoma and brain glioma tumors. Notably, it is found that D-Fe O SPs have 7.7-fold higher affinity for the tumor cell surface receptor cluster-of-differentiation 47 (CD47) than L-Fe O SPs. These findings uncover that chiral Fe O SPs act as a highly effective MRI contrast agent for targeting and imaging broad tumors, thus accelerating the practical application of chiral nanomaterials and deepening the understanding of chirality in biological and non-biological environments.