Bilirubin (BR) is clinically confirmed as a biomarker for liver health and is used to assess the prognosis of cirrhosis. Optical and chemical methods have been utilized for blood BR biosensing. While optical methods offer real-time monitoring and are handy and immune to infection, measurements may not be practical due to the instrument complexity and space requirements. This study investigated the dual-wavelength (DWL) technique for BR estimation using a system-on-chip (SoC). The SoC includes an optical module with blue (455 nm) and green (530 nm) LEDs which were used for DWL measurement. Porcine blood was used as a surrogate of human blood and BR levels were kept within the pathophysiological ranges projected from healthy individuals (<1.2 mgdL) to a cirrhotic patient (up to 50 mg/dL). Our findings show a high BR sensitivity in blood and this lays the groundwork for point-of-care testing for BR levels primarily for hyperbilirubinemia infants and cirrhotic adults out in homes or in-community settings.