The study examines the binding affinities and pharmacological potential of synthesized metal compounds with PfNDH2 in Plasmodium falciparum. So as to identify the combatting agent for malaria, six new organotellurium (IV) complexes (8a–8f) were prepared through a condensation reaction of 3‐methyl‐2‐thiophene carboxaldehyde and p‐nitroaniline. The synthesized compounds were inclusively characterized through physical and spectral techniques signifying a distorted octahedral geometry. The reported complexes were screened for antimalarial and antioxidant activities and analyzed using micro assays and DPPH assays, respectively. Using docking interactions, the research evaluates the binding energies, hydrogen bonds, and steric interactions of various compounds with PfNDH2, aiming to identify promising candidates for antimalarial drug development. Among the compounds, 8f showed the strongest binding affinity, with the lowest binding energy of −135.626 kcal/mol, and diverse hydrogen bonds with the target enzyme. Structure‐based pharmacophore modeling revealed critical interaction profiles and selectivity scores for the compounds, with 8f emerging as a promising candidate. Molecular electrostatic potential (MESP) analysis offered insights into the distribution of electron density within the compounds, influencing their reactivity and potential as antimalarial agents. ADMET analysis highlighted the pharmacokinetic and toxicological profiles of the compounds, revealing critical aspects for optimizing safety and efficacy. Overall, the findings provide valuable information for further development and optimization of potential antimalarial drugs.