Melatonin is a hormone produced in and secreted by the pineal gland. Besides its role in
regulating circadian rhythms, melatonin has a wide range of protective functions in the central
nervous system (CNS) disorders. The mechanisms underlying this protective function are associated
with the regulatory effects of melatonin on related genes and proteins. In addition to messenger
ribonucleic acid (RNA) that can be translated into protein, an increasing number of non-coding
RNAs in the human body are proven to participate in many diseases. This review discusses the
current progress of research on the effects of melatonin modulation of non-coding RNAs
(ncRNAs), including microRNA, long ncRNA, and circular RNA. The role of melatonin in regulating
common pathological mechanisms through these ncRNAs is also summarized. Furthermore, the
ncRNAs, currently shown to be involved in melatonin signaling in CNS diseases, are discussed.
The information compiled in this review will open new avenues for future research into melatonin
mechanisms and provide a further understanding of ncRNAs in the CNS.