Purpose: The aim of the study was to assess the comparative analysis of natural vs. synthetic antioxidants in Nigeria. Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: The study indicated that natural antioxidants, derived from plant sources such as fruits, vegetables, and herbs, are often preferred for their bioavailability and health benefits, including their ability to neutralize free radicals and reduce oxidative stress. They are associated with lower toxicity and potential health-boosting properties, such as reducing the risk of chronic diseases. On the other hand, synthetic antioxidants, which are chemically manufactured, tend to have a more stable and consistent potency, making them more effective in industrial applications like food preservation. However, concerns about their long-term health effects, including potential toxicity and adverse side effects, have led to a growing preference for natural alternatives. While both types play important roles in protecting cells from damage, natural antioxidants are often seen as safer, though their effectiveness can vary depending on the source and concentration. Implications to Theory, Practice and Policy: Free radical theory of aging, phytochemical hypothesis and toxicology of food additives may be used to anchor future studies on the comparative analysis of natural vs. synthetic antioxidants in Nigeria. In practical terms, health professionals should advocate for the incorporation of natural antioxidants into dietary guidelines, emphasizing foods rich in these beneficial compounds, such as fruits, vegetables, and herbs. From a policy perspective, there is a pressing need for regulatory frameworks that impose stricter guidelines on the use of synthetic antioxidants in food products, prioritizing safety assessments and considering long-term health impacts.