While 5-fluorouracil continues to be the chemotherapeutic gold-standard for the treatment of colon cancer, the side effects of 5-FU are numerous due to its ability to attack both healthy and cancerous cells. However, research continues to provide positive findings in regards to antioxidants and their success in deterring certain disease processes, especially cancer. Epigallocatechin-3-gallate (EGCG), the most abundant catechin found in green tea, is a valuable scavenger of reactive oxygen species in vitro as well as in vivo. Thymoquinone (TQ), the major active component of Nigella sativa (black seed), is also known for its powerful scavenger abilities as an inhibitor of oxidative stress and has been utilized in the Middle East for centuries because of its capability to heal many different diseases. Therefore, the objective of this study was to investigate the role of sustained drug delivery of TQ, EGCG, and 5-FU on the metabolic activity as well as structural changes in the SW-626 human colon cancer cell line in culture. Results of this study indicate a sustained drug delivery of EGCG and TQ demonstrated significant (p < 0 .01) cellular destruction and interference of cellular metabolic functions of SW-626 human colon cancer cells, which was comparable to SW-626 cells exposed to sustained drug delivery of 5-FU. Furthermore, MDA, glutathione, and nitric oxide all revealed significant alterations (p<0.05) as early as 24 hours. Morphologically, cellular changes occurred after exposure to TQ and EGCG at 24 hours which were also comparable to cells exposed to 5-FU. The delivery of the natural agents may offer a safe alternative treatment in for colon cancer.