This review delves into the role of Dickkopf-3 (DKK3), a secreted glycoprotein and member of the Dickkopf family, in non-malignant diseases. DKK3 is particularly known for its regulatory effects on the Wnt signaling pathway, a critical mediator in various biological processes including cell proliferation, differentiation, and migration. Our review highlights DKK3's influence in disorders of the cardiovascular, respiratory, renal, and muscular systems, where it contributes to disease progression by modulating these key biological processes. As an emerging biomarker, DKK3's levels have been found to correlate with various disease states, underscoring its potential diagnostic and therapeutic implications.