Traditional metal-based magnetic resonance imaging contrast agents (MRI CAs), such as gadolinium, iron, and manganese, have made significant advancements in diagnosing major diseases. However, their potential toxicity due to long-term accumulation in the brain and bones raises safety concerns. In contrast, non-metallic MRI CAs, which can produce a nuclear magnetic resonance effect, show great promise in MRI applications due to their adaptable structure and function, good biocompatibility, and excellent biodegradability. Nevertheless, the development of non-metallic MRI CAs is slow due to the inherent low magnetic sensitivity of organic compounds, their rapid metabolism, and susceptibility to reduction. Designing effective multifunctional organic compounds for high-sensitivity MRI remains a challenge. In this discussion, the mechanisms of various non-metallic MRI CAs are explored and an overview of their current status, highlighting both their advantages and potential drawbacks, is provided. The key strategies for creating high-performance MRI CAs are summarized and how different synthetic approaches affect the performance of non-metallic MRI Cas is evaluated. Last, the challenges and future prospects for these promising non-metallic MRI CAs are addressed.