Serpentine microchannel heat exchangers have extensive application potential owing to their compact structures and high heat-transfer coefficients. Existing studies on two-phase flow in serpentine channels have mostly used conventionally sized channels and focused on their curved sections. The analysis of the two-phase-flow pressure drop in serpentine microchannels cannot provide a complete theoretical explanation for practical applications. In this study, two-phase pressure drop in a serpentine microchannel with a hydraulic diameter of 0.65 mm and curvature radii of 1.2 mm, 1.8 mm, and 2.4 mm is experimentally investigated. Based on the experimental results, the proportion of pressure drop is calculated when the mass flow rate is 600 kg/(m²·s). The pressure drop changes were analyzed at mass flow rates of 600 kg/(m²·s), 1200 kg/(m²·s), 1800 kg/(m²·s), and 2400 kg/(m²·s). Experimental data were compared with existing empirical two-phase-flow pressure-drop correlations; however, they showed poor agreement.