Abstract Magnetic nanoparticles (MNPs) are promising tools for biomedical applications, particularly in molecular imaging using magnetic resonance imaging (MRI). The unique magnetic properties of MNPs, combined with their similarity in size to biological objects, make them ideal candidates for in situ imaging probes. The present study explores the use of magnetic nanoparticles (MNPs) as contrast agents in magnetic resonance imaging (MRI) for improved diagnostic accuracy. Specifically, the study investigates the MR contrast properties of polyethylene glycol-coated gadolinium oxide nanoparticles (PEG@GONPs) in five different biological fluids. The nanoparticles were synthesized using the polyol route and their size, shape, and morphology were characterized using TEM, SEM, and FT-IR spectroscopy. The magnetic resonance (MR) relaxivity of PEG@GONPs was studied in different biologically relevant media, and results revealed highest relaxivity in plasma as compared to other media. In addition, comparative analysis of proton relaxivity of the synthesized nanoparticles was carried out with a well-known gadolinium-based contrast agent, Omniscan, in various medium. The present findings revealed that PEG@GONPs can serve as an effective contrast agent for MRI imaging in biological fluids such as plasma, which is crucial for preclinical diagnosis of specific diseases and lesions. The high relaxivity observed in plasma could be attributed to the interaction of the nanoparticles with plasma proteins, amplifying their magnetic properties which further improve their ability to produce contrast in MR images.