Superparamagnetic iron oxide nanoparticles (SPIONs) are commonly used as magnetic resonance imaging (MRI) probes/contrast agents in clinical diagnosis because they can significantly improve the sensitivity of MRI. Polymers including natural and synthetic polymers with good biosafety and abundant surface groups are ideal surface coating for SPIONs to overcome their drawbacks such as poor colloidal stability, low relaxivity, and lack of functionality. Several SPIONs' structural properties such as crystal shape and size, charge, shell thickness, and cluster determine their relaxivity, biosafety, and in vivo imaging effect. Therefore, the rational design of SPIONs probes must explore the relationship between polymer structure and SPION properties. In this review, key structural properties of polymers such as surface groups, molecular weight, hydrophilicity, and grafting density are discussed for their effects on key properties of SPIONs. Additionally, some special polysaccharides, polypeptides, and antibodies can be used as targeting molecules to improve the imaging specificity of SPIONs, which is also briefly discussed in this review.