The determination of appropriate dietary strategies for the prevention of chronic degenerative diseases, cancer, diabetes, and cardiovascular diseases remains a challenging and highly relevant issue worldwide. Epidemiological dietary interventions have been studied for decades with contrasting impacts on human health. Moreover, research scientists and physicians have long debated diets encouraging alcohol intake, such as the Mediterranean and French-style diets, with regard to their impact on human health. Understanding the effects of these diets may help to improve in the treatment and prevention of diseases. However, further studies are warranted to determine which individual food components, or combinations thereof, have a beneficial impact on different diseases, since a large number of different compounds may occur in a single food, and their fate in vivo is difficult to measure. Most explanations for the positive effects of Mediterranean-style diet, and of the French paradox, have focused largely on the beneficial properties of antioxidants, among other compounds/metabolites, in foods and red wine. Wine is a traditional alcoholic beverage that has been associated with both healthy and harmful effects. Not withstanding some doubts, there is reasonable unanimity among researchers as to the beneficial effects of moderate wine consumption on cardiovascular disease, diabetes, osteoporosis, and longevity, which have been ascribed to polyphenolic compounds present in wine. Despite this, conflicting findings regarding the impact of alcohol consumption on human health, and contradictory findings concerning the effects of non-alcoholic wine components such as resveratrol, have led to confusion among consumers. In addition to these contradictions and misconceptions, there is a paucity of human research studies confirming known positive effects of polyphenols in vivo. Furthermore, studies balancing both known and unknown prognostic factors have mostly been conducted in vitro or using animal models. Moreover, current studies have shifted focus from red wine to dairy products, such as cheese, to explain the French paradox. The aim of this review is to highlight the contradictions, misconceptions, and scientific facts about wines and diets, giving special focus to the Mediterranean and French diets in disease prevention and human health improvement. To answer the multiplicity of questions regarding the effects of diet and specific diet components on health, and to relieve consumer uncertainty and promote health, comprehensive cross-demographic studies using the latest technologies, which include foodomics and integrated omics approaches, are warranted.