With the acceleration of aging society, delaying aging or promoting healthy aging has become a major demand for human health. 5-Lipoxygenase (5-LOX) is a key enzyme catalyzing arachidonic acid into leukotrienes (LTs), which is a potent mediator of the inflammatory response. Previous studies showed that abnormal activation of 5-LOX and overproduction of LTs are closely related to the occurrence and development of aging-related inflammatory diseases. Therefore, inhibiting 5-LOX activation is a possibly potential strategy for treating age-related diseases. In this paper, the latest research progress in 5-LOX activation, 5-LOX in mediating aging-related diseases and its small molecule inhibitors is briefly reviewed to provide scientific theoretical basis and new ideas for the prevention and treatment of aging-related inflammatory diseases.