Nanomedicine has benefited from recent advances in chemistry and biomedical engineering to produce nanoscale materials as theranostic agents. Well-designed nanomaterials may present optimal biological properties, influencing circulation, retention, and excretion for imaging and treatment of various diseases. As the understanding of nanomedicine pharmacokinetics expands continuously, efficient renal clearance of nanomedicines can significantly increase the signal-to-background ratio for precision diagnosis and lower potential toxicity for improved treatment. Studies on nanomaterial-kidney interactions have led to many novel findings on the underlying principles of nanomaterial renal clearance, targeting, and accumulation. In return, the optimized nanomedicines confer significant benefits to the detection and treatment of kidney dysfunction.In this Account, we present an overview of recent progress in the development of nanomaterials for kidney theranostics, aiming to speed up translation and expand possible applications. We start by introducing biological structures of the kidney and their influence on renal targeting, retention, and clearance. Several key factors regarding renal accumulation and excretion, including nanomaterial types, sizes, and shapes, surface charges, and chemical modifications, are identified and discussed. Next, we highlight our recent efforts investigating kidney-interacting nanomaterials and introduce representative nanomedicines for imaging and treatment of kidney diseases. Multiple renal-clearable and renal-accumulating nanomedicines were devised for kidney function imaging. By employing renal-clearable nanomedicines, including gold nanoparticles, porphyrin polymers, DNA frameworks, and polyoxometalate clusters, we were able to noninvasively evaluate split renal function in healthy and diseased mice. Further engineering of renal-accumulating nanosystems has shifted attention from renal diagnosis to precision kidney protection. Many biocompatible nanomedicines, such as DNA origami, selenium-doped carbon quantum dots, melanin nanoparticles, and black phosphorus have all played essential roles in diminishing excessive reactive oxygen species for kidney treatment and protection. Finally, we discuss the challenges and perspectives of nanomaterials for renal care, their future clinical translation, and how they may affect the current landscape of clinical practices. We believe that this Account updates our current understanding of nanomaterial-kidney interactions for further design and control of nanomedicines for specific kidney diagnosis and treatment. This timely Account will generate broad interest in integrating nanotechnology and nanomaterial-biological interaction for state-of-the-art theranostics of renal diseases.