Cell membrane cloaking is an important biomimetic approach for improving drug residence time in the body due to its distinctive concealment ability, making it highly biocompatible and efficient for targeted drug delivery. Leukocytes are considered a fundamental part of the immune system. Leukocyte membrane cloaked nanoparticles offer site-specificity and can escape the opsonization process besides enhanced systemic circulation time. This review emphasizes the anatomical and physiological features of different leukocytes in addition to the preparation and characterization of leukocyte membrane cloaked nanoparticles. It also covers the recent advancements of this biointerfacing platform in cancer therapy, inflammatory disorders, multifunctional targeted therapy and hybrid membrane-coated nanoparticles. However, leukocytes are complex, nucleated cell structures and isolating their membranes poses a greater difficulty. Leukocyte membrane cloaking is an upcoming strategy in the infancy stage; nevertheless, there is immense scope to explore this biomimetic delivery system in terms of clinical transition, particularly for inflammatory diseases and cancer.