Polyphenols are nutrients that are classified as phytochemicals because they are found exclusively in foods of plant origin. They are divided into flavonoids (flavonols, flavones, isoflavones, anthocyanins, flavon-3-ols, and flavones) and nonflavonoids (phenolic acids, stilbenes, lignans, dihydrochalcones, and coumarins). Research shows that polyphenols have multiple positive health effects. This paper aims to systematize recent scientific results on the effects of polyphenols on health. A search of the scientific literature of the last 20 years in the English language on the health effects of polyphenols was performed in the "PubMed" database using the keywords: "polyphenols"; "microbiota"; "diabetes mellitus"; "cardiovascular diseases"; "cognitive functions"; "viral diseases"; "cancer"; "mental health" and "dyslipidemias". There is a mutual positive influence of polyphenols and microbiota. Polyphenols affect the composition of the microbiota, especially the growth of beneficial microbiotic strains. In epidemiological studies, polyphenols have shown a protective effect concerning DM type 2 by lowering blood glucose and glycosylated hemoglobin, reducing insulinemia and increasing insulin sensitivity, reducing inflammation and oxidative stress in cells. By reducing arterial stiffness, oxidative stress, inflammation, and endothelial dysfunction, and regulating the production of nitrogen monoxide and cytokines, they reduce the risk of hypertension, myocardial infarction, and cerebral insult. Polyphenols have a positive effect on cognitive functions and executive functioning and reduce the risk of Parkinson's disease. Their antiviral effect is based on the inhibition of the enzyme helicase, which is necessary for viral replication and recombination, reduction of oxidative stress, virucidal effect, interaction with the structural proteins of the virus, and interference with the fusion of the virus with the cell membrane, reduction of inflammation and increase of immunity and reduction of dysbiosis in the intestines and lungs. The protective effect of polyphenols concerning cancer is based on induced apoptosis, inhibition of the matrix-metalloproteinase enzyme that enables metastases, inhibition of tumor growth, and inhibition of angiogenesis. In terms of mental health, polyphenols reduce the risk of depression and ADHD (Attention Deficit Hyperactivity Disorder) and have a beneficial effect on the reduction of tardive dyskinesia in patients with schizophrenia. They also have a positive effect on dyslipidemia, by reducing the level of LDL cholesterol and increasing the level of HDL cholesterol. Polyphenols are phytochemicals with multiple positive health effects. They work synergistically with the gut microbiota. Epidemiological studies have shown that polyphenols reduce the risk of diabetes mellitus type 2, hypertension, myocardial infarction, cerebral insult, viral diseases, Parkinson's disease, cognitive disorders, cancer, depression, and dyslipidemia. Nutritional support or supplementation with polyphenols can be recommended in the primary and secondary prevention of the mentioned diseases.