The research progress in fatigue protocols and biomechanics of lower extremity and its relationship with injury induced by exercise-induced fatigue was reviewed in this paper. At present, fatigue protocols can be divided into the traditional fatigue-induced protocol and the functional fatigue-induced protocol under laboratory condition. The former mainly includes power-cycling model, treadmill run model and step-ups model, while the latter is closer to what is experienced during competition, which is usually shown as multidirectional movements. In addition, the biomechanical measures of exercise-induced fatigue mainly include kinematics, ground reaction force, joint mechanics and electromyography. Different fatigue protocols do not uniformly produce alterations in lower limb biomechanical factors. The refinement of fatigue protocols and specific indicators should be considered in future studies, in order to compare the induced effects of fatigue protocols and provide references for the selection of fatigue protocols in laboratory tests. Meanwhile, the relationship between the response of brain-nerve system and the activation of musculoskeletal system for specific athletic task should be focused, so as to understand the difference of biomechanical mechanisms between fatigue protocols and further explore the effect of exercise-induced fatigue on sports injuries.