The present study basically examines thermal performance and relevant flow phenomena of a flat plate closed-loop pulsating heat pipe (FP-CLPHP) filled with binary mixtures. The heat pipe has eight turns, each of which consisting of asymmetrical channel pairs having cross sections as 2 mm × 2 mm and 1 mm × 2 mm (width × height). Binary mixtures are generated as mixtures of ethanol (E) and pentane (P) with different mixing ratios. Mainly, effects of volume mixing ratio (E/P = 1:1, 1:3 and 3:1), vertical (90°) and horizontal orientation (0°) and filling ratio (30% and 60%) on thermal characteristics are investigated under different heat inputs. For examination of flow dynamics, images are obtained by using a high-speed camera at 1000 fps. The results show that variation of volumetric percentage of each component significantly changes thermal performance. Increasing pentane in the mixture improves the thermal performance, such that heat pipe with mixing ratio of E/P = 1:3 can properly operate even at horizontal position. On the other hand, increasing volume of ethanol in mixture leads to collapse of the FP-CLPHP at both orientations (0° and 90°). Generally, the filling ratio of 30% shows better thermal performance. Complex bubble–liquid interactions and dynamics play critical roles on thermal characteristics. Two novel characteristic phenomena are identified for non-uniform PHPs: (1) flooding phenomenon and (2) asymmetrical rapid bubble growth phenomenon.