Natural caffeine is found in many plants, including coffee beans, cacao beans, and tea leaves. Around the world, many beverages, including coffee, tea, energy drinks, and some soft drinks, have this natural caffeine compound. This paper reviewed the results of meta-studies on caffeine's effects on chronic diseases. Of importance, many meta-studies have shown that regularly drinking caffeine or caffeinated coffee significantly reduces the risk of developing Alzheimer's disease, epilepsy, and Parkinson's disease. Based on the health supplements of caffeine, this review summarizes various aspects related to the application of caffeine, including its pharmacokinetics, and various functional health benefits of caffeine, such as its effects on the central nervous system. The importance of caffeine and its use in alleviating or treating cancer, diabetes, eye diseases, autoimmune diseases, and cardiovascular diseases is also discussed. Overall, consuming caffeine daily in drinks containing antioxidant and neuroprotective properties, such as coffee, prevents progressive neurodegenerative diseases, such as Alzheimer's and Parkinson's. Furthermore, to effectively deliver caffeine to the body, recently developed nanoformulations using caffeine, for instance, nanoparticles, liposomes, etc., are summarized along with regulatory and safety considerations for caffeine. The U.S. Department of Agriculture (USDA) and the Food and Drug Administration (FDA) recommended that healthy adults consume up to 400 mg of caffeine per day or 5~6 mg/kg body weight. Since a cup of coffee contains, on average, 100 to 150 mg of coffee, 1 to 3 cups of coffee may help prevent chronic diseases. Furthermore, this review summarizes various interesting and important areas of research on caffeine and its applications related to human health.