Fatigue, characterised by lack of energy, mental exhaustion and poor muscle endurance which do not recover following a period of rest, is a common characteristic symptom of several conditions and negatively impacts the quality of life of those affected. Fatigue is often a symptom of concern for people suffering from conditions such as fibromyalgia, chronic fatigue syndrome, cancer, and multiple sclerosis. Vitamins and minerals, playing essential roles in a variety of basic metabolic pathways that support fundamental cellular functions, may be important in mitigating physical and mental fatigue. Several studies have examined the potential benefits of nutrients on fatigue in various populations. The current review aimed to gather the existing literature exploring different nutrients’ effects on fatigue. From the searches of the literature conducted in PubMed, Ovid, Web of Science, and Google scholar, 60 articles met the inclusion criteria and were included in the review. Among the included studies, 50 showed significant beneficial effects (p< 0.05) of vitamin and mineral supplementation on fatigue. Altogether, the included studies investigated oral or parenteral administration of nutrients including Coenzyme Q10, L-carnitine, zinc, methionine, nicotinamide adenine dinucleotide (NAD), and vitamins C, D and B. In conclusion, the results of the literature review suggest that these nutrients have potentially significant benefits in reducing fatigue in healthy individuals as well as those with chronic illness, both when taken orally and parenterally. Further studies should explore these novel therapies, both as adjunctive treatments and as sole interventions.