The development of chemopreventive approaches using a concoction of phytochemicals is potentially viablefor combating many types of cancer including colon carcinogenesis. This study evaluated the anti-proliferativeeffects of ginger and Gelam honey and its efficacy in enhancing the anti-cancer effects of 5-FU (5-fluorouracil)against a colorectal cancer cell line, HCT 116. Cell viability was measured via MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphenyl)-2H-tetrazolium) assay showing ginger inhibiting the growthof HCT 116 cells more potently (IC50 of 3mg/mL) in comparison to Gelam honey (IC50 of 75mg/mL). Combinedtreatment of the two compounds (3mg/mL ginger+75mg/mL Gelam honey) synergistically lowered the IC50 ofGelam honey to 22mg/mL. Combination with 35 mg/mL Gelam honey markedly enhanced 5-FU inhibitingeffects on the growth of HCT 116 cells. Subsequent analysis on the induction of cellular apoptosis suggestedthat individual treatment of ginger and Gelam honey produced higher apoptosis than 5-FU alone. In addition,treatment with the combination of two natural compounds increased the apoptotic rate of HCT 116 cells dosedependentlywhile treatment of either ginger or Gelam honey combined with 5-FU only showed modest changes.Combination index analysis showed the combination effect of both natural compounds to be synergistic in theirinhibitory action against HCT 116 colon cancer cells (CI 0.96 < 1). In conclusion, combined treatment of Gelamhoney and ginger extract could potentially enhance the chemotherapeutic effect of 5-FU against colorectal cancer.