Background Sickle Cell Disease (SCD) presents a significant global health burden, characterised by inflammation and oxidative stress, contributing to its complex pathophysiology and substantial socioeconomic implications. Omega-3 has been shown to alleviate SCD and has been found to be richly available in traditional medicinal plants such as perilla seed, sea buckthorn and amaranth. Objective This research highlights the potential of omega-3 fatty acid supplementation as a therapeutic intervention for SCD. Methods We conducted an extensive search across databases such as PubMed, MEDLINE, and Google Scholar to gather pertinent articles that explore the effect of omega-3 fatty acid on inflammatory and oxidative stress markers in SCD. Keywords such as oxidative stress, and inflammation were also used in the search. Omega-3 fatty acids, particularly EPA and DHA, exhibit anti-inflammatory and antioxidant properties that hold promise in mitigating these pathological processes. Results Clinical studies demonstrate reductions in pain episodes, hospitalisations, and oxidative stress markers with omega-3 supplementation, indicating its therapeutic efficacy. Conclusion Further research is needed to determine optimal dosage, duration, and population-specific considerations. Comparative effectiveness studies and long-term safety assessments are essential for informing clinical practice. Integrating omega-3 supplementation into comprehensive treatment regimens alongside other modalities may offer a holistic approach to managing SCD. Overall, ongoing research efforts in omega-3 fatty acid supplementation offer hope for optimizing treatment strategies and improving outcomes for individuals affected by SCD.