This paper presents the results of the development of innovative sandwich panels made by combining wood bio-concretes and long sisal fibers reinforced composites. An experimental study of the wood bio-concretes (WBC) was carried out by producing several cement-to-wood ratios (0.5, 1, 2, 2.5 and 3) in order to allow the development of panels of different density. Before producing the WBC, the influence of hot water washings of the wood shavings on the cement hydration was investigated. The effect of the cement-to-wood ratios on the density, thermal conductivity, compressive strength and elastic modulus of the WBC were also investigated. Lightweight bio-concretes were obtained with densities ranging between 700 and 1250 kg/m3 and compressive strengths within 0.44–16 MPa, after 28 days cure. The lighter and denser bio-concretes were used as cores in sandwich system with faces made of cement composites reinforced with 6% of long sisal fibers distributed in three layers. The results of compressive and flexural tests performed on the sandwich specimens revealed that the WBC2.5 were more effective in terms of promoting compressive strength, shear transfer capacity and allowing a pure bending failure, while WBC0.5 promoted core shear cracks and the inferior face crush.