Retinoic acid-related orphan receptor (ROR) is implicated in modulating a variety of physiological processes, including cerebellar development, lymphoid tissue development, retinal development, bone formation, lipid metabolism, circadian rhythm, oxidative stress, and inflammation suppression. Furthermore, ROR is also a promising therapeutic target for autoimmune diseases, tumours, obesity, diabetes, and other diseases. Melatonin (N-acetyl-5-methoxytryptamine) is an evolutionary molecule found in bacteria, fungi, algae, plants, invertebrates, and vertebrates. It regulates multiple functions that have developed along the evolutionary timescale. In humans, melatonin is pleiotropic [5]. Melatonin modulates sleep-wake rhythms, reproduction, and bone metabolism; it also affects the immune, neurological, cardiovascular, digestive, urinary, and endocrine systems. Moreover, it exhibits anti-inflammatory, antioxidant, anti-infective, and anti-tumour properties while also being a potential therapeutic agent for obesity, cardiovascular diseases, and neurodegenerative disorders. A debate is ongoing on whether ROR is a nuclear receptor of melatonin.