Malaria, caused by Plasmodium protozoa transmitted through mosquito bites, remains a significant global health concern despite extensive control efforts. The rise and dissemination of drug-resistant strains of the malaria parasite pose a substantial threat to human health. Therefore, there is an urgent need to explore alternative drug targets and develop effective antimalarial agents. This study aims to investigate the potential of macrolide molecules as promising candidates to combat drug resistance and reduce malaria-related mortality. Using in silico approaches, macrolide molecules were selected based on their binding scores and protein-ligand interactions. The selected molecules underwent further analysis to assess their pharmacokinetic profiles and toxicity using computational methods. These investigations contribute valuable insights into important drug parameters. By leveraging the recognized pharmacophore structure, the design of novel antimalarial drugs can be optimized. The findings of this study provide new avenues for research and development of macrolide-based antimalarial agents. These molecules hold the potential to overcome drug resistance and offer improved therapeutic outcomes. Through this in silico evaluation, a pharmacological perspective is presented to explore the antimalarial efficacy of macrolide molecules. By identifying new drug targets and developing lead compounds, this research offers a promising approach to addressing the global burden of malaria and reducing associated mortality rates. Further experimental validation is warranted to validate the potential of these macrolide molecules as effective antimalarial agents.