The Kindlin protein family, consisting of Kindlin-1, Kindlin-2, and Kindlin-3, is crucial in cellular physiology and pathology. Traditionally recognized as essential co-activators of integrins, Kindlins regulate integrin-dependent adhesion, migration, and signal transduction across diverse cell types. Recent advances, however, have revealed that Kindlins extend beyond integrin activation, participating in non-integrin-dependent signaling pathways and transcriptional regulation. This review provides a comprehensive summary of structural, physiological, and pathological roles of Kindlins, integrating their classical integrin-dependent and emerging integrin-independent functions. In this review, we a) offer a comprehensive overview of the structural and functional roles of Kindlin proteins across various organ systems; b) highlight their integrin-independent signaling functions and exact regulatory mechanisms; c) discuss their contributions to pathologies and explore the potential of Kindlins as biomarkers and therapeutic targets.