Drug-induced brain injury (DIBI) results from toxicity, interactions or misuse and is increasingly linked to gut-microbiota dysbiosis operating via the gut-brain axis. Disturbed microbial balance drives three core mechanisms-oxidative stress, neuroinflammation and metabolic dysfunction-leading to blood-brain barrier leakage, neuronal loss and cognitive impairment; antibiotics, antineoplastics and psychoactive drugs further promote bacterial translocation and systemic inflammation. Microbial metabolites and neurotransmitters also mediate post-injury anxiety and depression. Restoring microbial equilibrium with probiotics, prebiotics or microbiota transplantation attenuates these pathways and offers a promising therapeutic strategy for DIBI.