A novel caudal-fin-inspired hourglass-shaped self-agitator installed inside a plate-fin heat exchanger has been experimentally investigated to characterize its thermo-hydraulic performance. Because of fluid-structure interaction between the air and the caudal-fin-inspired hourglass-shaped self-agitator, there is periodic conversion between fluid kinetic energy and elastic strain energy. Vortices generated by the self-sustained vibration of the self-agitator enhance flow mixing and thus heat transfer performance. Experiments were conducted at a wide range of Reynolds numbers from 400 to 10,000, which covered the laminar-transitional-turbulent regime. Experimental correlations of pressure drop as a function of a dimension parameter, friction factor, and Nusselt number have been proposed. Mutual coupling motions and effects of multiple-row flapping caudal-fin-inspired hourglass-shaped self-agitators in parallel and tandem configurations were studied by using a high-speed camera. A stereo Particle Image Velocimetry system was used to conduct detailed flow field measurements to quantify the flow mixing level. Parameter studies for the stream-wise distance (Le., the pitch) between the neighboring caudal-fin-inspired hourglass-shaped self-agitators have been investigated to exploit the best performance of the heat exchanger equipped with caudal-fin-inspired hourglass-shaped self-agitators. For the chosen plate-fin heat exchanger and assigned working conditions, the best heat transfer performance was obtained with twelve-row self-agitators with a pitch of 12.5 mm, which caused a 200% increase in the Nusselt number over the clean channel at the same Reynolds number. However, the best overall performance was obtained with six-row self-agitators with a pitch of 25 mm, which caused a 68% enhancement in thermal-hydraulic characteristics compared to the clean channel at the same Reynolds number.