Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with rapid progression after onset. At present, there are no effective drugs to delay the disease progression or improve its clinical symptoms. A large number of clinical practices have shown that intervention with traditional Chinese medicine can delay the progression of ALS and significantly improve the clinical symptoms of patients, but its mechanism is still unclear. In recent years, basic studies have found that the pathogenesis and progression of ALS are related to excitatory neurotoxicity, mitochondrial dysfunction, axoplasmic transport dysfunction, neurotrophic factor deficiency, microglia and astrocyte dysfunction. Traditional Chinese medicine may play a role in the treatment of ALS by intervening in the above ways. This paper points out that the established animal model of ALS can be used to study the multi-target molecular mechanism of traditional Chinese medicine in the treatment of ALS, and provide the basis of molecular biology and genetics for traditional Chinese medicine in the treatment of ALS.