Considering the causative or contributory effects of diabetes mellitus on common neurological diseases such as polyneuropathy, stroke and dementia, modern antidiabetic drugs may be expected to reduce incidence or progression of these conditions. Nevertheless, most observed benefits have been small, except in the context of therapy for diabetes mellitus type I and new-onset polyneuropathy. Recently, semaglutide, a GLP-1 analog, has been shown to significantly reduce stroke incidence in a randomized controlled trial. Beneficial effects of antidiabetic drugs on stroke severity or outcome have been controversial, though. The level of risk conferred by diabetes mellitus, the complex pathophysiology of neurological diseases, issues of trial design, side-effects of antidiabetic drugs as well as co-medication might be interacting factors that determine the performance of antidiabetic therapy with respect to neurological outcomes. It might be speculated that early treatment of prediabetes might prevent cerebral arteriosclerosis, cognitive decline or polyneuropathy more effectively, but this remains to be demonstrated.