<p>Encapsulation of protein-based drug carriers represents a promising strategy for enhancing therapeutic efficiency by improving stability, bioavailability, and controlled release. Protein nanoparticles, due to their inherent biocompatibility, biodegradability, tunable particle size and morphology, enriched surface properties, porosity, and high encapsulation efficiency, have attracted considerable attention as drug delivery carriers. Their ability to sustain therapeutic activity has been demonstrated in the treatment of neurological disorders, infections, tumors, and cancer. A wide range of proteins, including albumin, gliadin, gelatin, zein, ferritin, and silk fibroin, have been investigated using diverse encapsulation strategies such as coacervation, self-assembly, emulsification, and ionotropic gelation. This review discusses the chemical and structural properties of protein nanoparticles, highlights recent advances in encapsulation methodologies, demonstrates the key parameters that enhance the loading and release efficiency, and analyzes drug stabilization, loading, and release profiles in relation to therapeutic performance. While protein-based delivery systems offer significant advantages, challenges such as enzymatic degradation of drugs, sensitivity to pH fluctuations, and the selectivity of protein carriers continue to limit clinical translation. In summary, this review emphasizes the potential of protein nanoparticle encapsulation to improve drug design, loading efficiency, and release behavior, thereby opening new opportunities for the development of safer and more effective therapeutic systems. At the same time, it highlights the importance of addressing existing barriers through continued research to visualize the clinical impact of protein-based drug delivery platforms.</p> Graphical Abstract <p></p>