Using medicinal chemistry and in vivo experimental approaches, we demonstrate that select TYRO3 agonism markedly improves kidney function and attenuates podocyte injury in experimental models of DKD and FSGS and that small-molecule TYRO3 agonists, such as compound 10 (C-10) described in this study, can be further developed as specific therapy for glomerular disease. Here, TYRO3 is linked to diabetic kidney disease.