One of the most dreadful diseases in Asia, Africa, and Latin America is malaria, which over the decades has been highly fatal when not controlled at an early stage and when not managed properly. Even though there are multiple categories of anti-malarial drugs available on the market, one of the most common demerits of such drugs is that most of them face the major challenge of complete absorption via oral route. This is due to either the first-pass effect or the poor delivery system, which does not deliver the drugs completely until the site of action. The current study emphasizes the study of the preparation of different lipid-based formulations and comparative assessments of their percent drug release. Hence, for the research purpose, four anti-malarial drugs (i.e., artemisinin, amodiaquine, halofantrine, and chloroquine) are well known for being highly lipophilic in nature and having the least affinity for polar solvents like water, because of which they are least soluble in aqueous media and solvents. The oral absorption of such drugs is a challenge, and hence they face poor oral bioavailability due to their limited aqueous solubility. In the absorption process of such drugs, the solubility remains at its "rate-limiting step." The research study discusses the preparation of different lipid formulations as it was believed that such molecules, which have limited aqueous solubility and exhibit positive food effects (i.e., an increase in absorption post-intake of food), have a better chance of enhanced oral absorption due to the formation of in-situ micelles that get absorbed via the lymphatic circulatory system. The current research study primarily focuses on studying the percent drug release of such anti-malarial drugs across a wider physiological range of pH, i.e., in the acidic region pH ~1, ~2, and ~4.5, in the neutral range pH~6.8, and in the alkaline range pH ~7.4, including simulated fasted-state gastric fluid, simulated fasted-state intestinal, simulated fed-state gastric fluid, simulated fed-state intestinal fluid, lipolytic digestive medium, and purified water. The formulations wherein lipids were used exhibited the highest percent drug release in bio-relevant simulated gastric, intestinal, and lipolytic digestive media when compared to formulations wherein there were no lipids. The study indicated that such lipoidal formulations tend to solubilize and therefore exhibit a higher percentage of drug release because the drug undergoes solubilization in the presence of surfactants present in the medium, e.g., sodium taurocholate. All lipoidal formulations selected in the study exhibited a similar trend and solubilization effect when compared to formulations where no lipids were used.