The requirements of bio-composites for the structural applications are high strength and high stiffness. Due to the anisotropic nature of composite by the reinforcement of fiber, it is a challenging process to develop highly efficient composites. The optimized design criteria for the development of bio-composites depend on the life time expectancy of the components to be designed. Hence it is required to evaluate the composites failures at cyclic fatigue loading. In this work, fatigue failure of newly developed jute fiber reinforced hybrid polymer composites was analyzed to optimize the composition parameters. The hybrid polymer is prepared with the mixture of cashew nut shell liquid (CNSL) resin and polyester resin for the improvement of biocompatibility of the composite developed. The experimental investigations on various samples of composites give a promising solution for the fatigue failure of the specifically produced composite specimen.