Flexible and wearable sensors have attracted much attention for their applications in health monitoring and the human-machine interaction. The most studied wearable sensors have been demonstrated for sensing a limited range of metabolites such as ions, glucose, uric acid, lactate, etc. Both sweat and urine contain numerous other physiologically relevant metabolites indicative of health and wellness. This work demonstrates the use of the wearable sensor for the detection of β-hydroxybutyrate (HB) in sweat. HB is an important biomarker for diabetic ketoacidosis, a condition caused by the accumulation of ketone bodies in hyperglycemia or metabolic acidosis patients. Herein, we fabricated an integrated sensing system coupling an HB detection chamber with a serpentine electrode for sensing physiological signals such as pulse beat, vocal cord vibration, etc. The real-time HB detection was based on a β-hydroxybutyrate dehydrogenase enzymatic reaction. The stability of the enzyme and the cofactor couple was achieved by cross-linking networks and a redox mediator, thereby achieving high selectivity and low detection limits to HB in urine and sweat. The dual-functional sensor was integrated with a signal processing circuitry for signal transduction, conditioning, processing, wireless transmission, and real-time convenient health monitoring display to a smartphone via home-developed software.