Fractal structures in nature offer a unique "fractal contact mode" that guarantees the efficient working of an organism with an optimized style. Fractal nanostructured biointerfaces have shown great potential for the ultrasensitive detection of disease-relevant biomarkers from small biomolecules on the nanoscale to cancer cells on the microscale. This review will present the advantages of fractal nanostructures, the basic concept of designing fractal nanostructured biointerfaces, and their biomedical applications for the ultrasensitive detection of various disease-relevant biomarkers, such microRNA, cancer antigen 125, and breast cancer cells, from unpurified cell lysates and the blood of patients.