Grapes are fruits widely grown and known throughout the world, and they have significant economic and nutritional value. However, grapes are highly susceptible to attack by pests and insects, which reduces production and product quality. Pesticides are the most utilized solution for meeting global consumption demands and avoiding losses, and they can be used at any production stage. Although the benefits of using pesticides in grape production are evident, the prescribed limits must be observed to minimize their harmful effects on human health, as the accumulation of these compounds in the body over the long term can decrease life expectancy. This review of the literature intends to give a comprehensive analysis of pesticide residues in grape juice and wine, investigate analytical methodologies for pesticide detection, and set maximum residue limits (MRLs). Furthermore, the impacts of pesticide use and exposure to residues on the gut microbiota and adverse effects on human health were examined. Finally, insights into advances in detection and removal methods to mitigate the impact of pesticide residues in grape wine were presented. This review considers future perspectives in the field, including the development of safe and sustainable pesticides, with the improvement of international regulations to ensure food safety, aiming to expand pre-existing knowledge to provide more sustainable agricultural practices, encouraging global wine production. The target audience for this review includes researchers and academics, professionals in the agricultural and wine industry, regulators and government authorities, health professionals, and health and food safety-conscious consumers.