Human blood carries key physiological and pathological information. Quantification of blood components is essential for the diagnosis of many chronic diseases. Analyzing blood in the conventional laboratory setup requires expensive and bulky equipment, skilled personnel, and long processing time, which limits the capability of point-of-care (POC) diagnosis in emergencies. Lab-on-a-chip (LOC) diagnostic devices significantly reduce the sample size and analysis time, which drastically cut down the cost. Moreover, the integration of smartphone-based sensors allows direct data processing by using smartphone apps and wireless data transmission for remote analysis. This chapter provides a concise overview of the recent development of LOC devices for whole blood analysis. We mainly discuss the fabrication techniques and the working principle of the chips for blood cell separation, blood typing, and disease diagnosis in the POC platform. We also highlight the typical detection principles of the widely applied sensing modalities of smartphone-based LOC devices for detecting blood diseases.