Melatonin (MT) from plant species has attracted attention in the past decade. It is still the only conserved molecule that is broad spectrum as a regulator of biological functions since it has been identified in the unicellular alga, higher plants, and animals. In plants, MT is produced from tryptophan converted to tryptamine in the chloroplast. Subsequent pathways involve the conversion of tryptamine into serotonin, which can form methoxytryptamine and N-acetyl-serotonin resulting in MT. MT has been documented to play a crucial role in governing various aspects of plant growth and development, including the regulation of circadian rhythms and photoperiodic responses. Moreover, it has been found to contribute significantly to antioxidation and stress resistance in plants. Its use as an anti-inflammatory and immunomodulated drug against human diseases also gained significant attention in humans. There is an increasingly shared agreement that MT is valuable in maintaining body functions and homeostasis, particularly during adulthood, owing to its antioxidant, anti-inflammatory, and immunomodulatory properties. MT can mitigate symptoms such as cough, dyspnea, and fatigue and shorten hospitalization time in COVID patients. Moreover, it could reduce thrombotic and septic processes. In Alzheimer’s patients, it improves sleep quality and cognitive function. In Parkinson’s disease, it can enhance sleep quality and non-motor symptoms and reduce oxidant marker levels. In multiple sclerosis it improves sleep time and lowers fatigue scores and inflammatory and oxidative scenarios. In polycystic ovary syndrome, MT reduced insulin, HOMA, LDL-c, body weight, waist circumference, and TNF-α levels. In dermatitis, it led to fewer signs of dermatitis compared to placebo. It decreased the degree of liver fat compared to the placebo group in non-alcoholic fat liver disease.