<p>Drug abuse poses an enormous threat to global public health. Long-term drug abuse can reduce the quality of life of patients and increase the healthcare burden on society. There is growing interest in developing new methods to mitigate the effects of drug abuse. The gut microbiota plays a key role in maintaining homeostasis within the brain-gut-lung axis, which is critical in drug-abusing patients. The microbiota-brain-gut-lung axis refers to the interactions of microbes with the brain, gut, and lung. The effects of drug abuse on the gut microbiota are increasingly recognized, especially the pathogenesis by which the microbiota-brain-gut-lung axis is involved in regulating organ-organ communication, to explore new therapeutic approaches for clinical drug abuse. Currently, in addition to antibiotics, antiviral drugs, anti-tumor drugs, corticosteroids, drugs for the treatment of neurodegenerative diseases, and anesthetics also cause gut microbiota imbalance. This review summarizes the effects of drug abuse on gut microbiota and the important role of the microbiota-brain-gut-lung axis in drug abuse. Identifying changes in the gut microbiota associated with drug abuse and their underlying mechanisms under the principles of predictive, preventive, and personalized medicine (PPPM) is a critical step toward achieving PPPM. These strategies include FMT, probiotic supplements, and engineered bacteria that can benefit sub-healthy individuals with gut dysbiosis caused by drug abuse.</p>