Biological materials depict an excellent combination of both strength and toughness, which is a vital requirement for most engineering materials. It provides motifs to revolutionize the techniques for producing novel materials with improved properties. However, there is still a lack of deep understanding regarding the toughening mechanisms in biological materials, in order to overcome the conflict between strength and toughness in synthetic materials. This paper establishes a microstructure-based fracture model to reveal the toughening effect of the microcrack zone near the crack tip. Firstly, the stress–strain relationship considering the initiation and saturation of microcracks is derived. Then, a fracture mechanics model incorporating the micro-mechanics of microcracks is established, based on the above nonlinear mechanical response. Finally, the model is used to investigate the influence of microstructural parameters on the fracture toughness considering microcracks. The results show that there are two nondimensional parameters that significantly influence the fracture toughness: the ratio between the gap and overlapped zone, ξ, and λla. In addition, the selection of the microstructural parameters not only needs to consider the balance between stiffness, strength, and toughness, but also achieve the optimal toughness by combining the effects of several different mechanisms.