A number of biological molecules such as inflammatory enzymes and cytokines are altered during dengue virus (DENV) infection, many of which are attributed to the pathogenesis of the DENV infection. Papaya (Carica papaya) based extracts (PBE) and certain vitamins have been proven beneficial for dengue fever (DF) patients. The extract of papaya leaves were shown to improve platelet count in dengue patients. Extracts of papaya pulp based was also shown to induce in vitro IL-6 and stem cell factor in human peripheral blood mononuclear cells and stem cells of mesenchymal origin. Different vitamins such as D, E, and C have shown promise to treat dengue disease when taken in small supplementation trials. However, the exact molecular mechanisms on the beneficial roles of either PBE or vitamins are yet to be defined. Hence, the aim of this review is to link the cellular and molecular responses of DENV pathogenesis and pharmacological actions of the bio-active components of PBE or vitamins. It has also been shown that the beneficial roles of PBE and vitamins in DF are linked to thrombopoiesis, prevention of the viral entry and replication, decrease in oxidative damage assisted thrombocytopenia, and the reduction in vascular leakage. The DENV mediated fatalities are expected to expand it's geographic boundary whilst an efficient drug and the most likely candidate vaccine against DENV are still in progress. Findings on the molecular mechanisms of food and nutrient supplement might reinforce ongoing research to treat the increasing number of DENV infected patients using natural products while waiting for the right drug and vaccine.