In this study, our objective was to develop a photothermal biosensor (PTB) for measurement of C-reactive protein (CRP) concentrations in human saliva. The resulting PTB that we developed is rapid, simple, and minimally invasive, and can be used to measure the concentration of CRP in human saliva (7-μL sample volume). The CRP (0.1–100ng/mL) is captured by the sandwich immunoassay on the sensor, and gold nanoparticles (GNPs) conjugated with antibodies cause a photothermal effect when irradiated with a laser (90s, wavelength=532nm). The temperature changes caused by this effect correlate with the concentrations of CRP. Therefore, the sensor shows a higher correlation with the concentrations of CRP than commercial detection kits. Its detection limit is 0.1ng/mL CRP.