Traditional drug delivery strategies often have side effects due to uneven drug distribution leading to the subtherapeutic impacts. Ligand-modified nanoparticles offer a revolutionary approach to precise drug delivery. These modified nanoparticles can potentially target macrophages, which is crucial for defense and disease progression efficiently. Out of many classes of ligands, biomacromolecular ligands emerged as potential ligands for directing these nanoparticles to macrophages due to their consecutive receptors over the macrophage surface, assisting easy internalization and thus supporting elevated efficacy and reduced toxicity. This approach could significantly improve treatment for diseases like cancer, tuberculosis, etc. by directing drugs to macrophages and reducing side effects. By leveraging nanotechnology and biomacromolecular-based ligand-directed targeting, we can achieve more precise and effective treatments, paving the way for advancements in precision medicine.