###### Abstract  
Agro-industrial by-products and by-products from the wine industry (pomace, peels, leaves, stems, and seeds) represent a potential economic interest because they are usually relevant natural sources of bioactive compounds, which may present significant biological activities related to human health and well-being. This article aims to review wine and winery industry by-products as potential natural sources of antioxidant, antimicrobial, anti-inflammatory, antiaging, and anticancer compounds, as well as briefly highlighting the extraction methods used to obtain these bioactive compounds and explore their potential applications in the food, cosmetic, and packaging industries. Although there are some studies of wine industry by-products with different origins, this revision will be mainly focused on the Portuguese vineyard industry since it represents an import industrial sector as proof of the diversity of the bioactive compounds identified. Therefore, the recovery of these bioactive molecules that act as antioxidants and health-promoting agents may promote a variety of industries at the same time as the circular economy. by-products; efficiency; polyphenols; winemaking; circular economy +
Footnote †: journal: Applied Sciences  
and important agro-industries in the world. Every year, 259.9 million hl of wine are produced around the world, leading to the generation of 20 million tons of biological by-products [10,11]. For millennia, grapes have been a crucial fruit crop, revered by ancient civilizations for their role in the art of winemaking. They hold a special place in history as one of the oldest and most significant crops [12]. There exist about 2000 different grape varieties grown around the world. According to the International Organization of Vine and Wine (OIV), grape production in 2018 was 77.8 million tons globally. Of this production, 7% was converted to dried grapes, 36% were destined to be table grapes, and 57% of cultivated grapes have been used for winemaking processes [13,14]. Wine is one of the most widely produced beverages in the world, and its global production in 2018 was approximately 294 million hectolitres (MhL), while in 2020, 2021, and 2022, approximately 262, 260 [13] and 259.9 MhL were produced for each year, respectively [15]. Specifically for Europe, in 2021, the top five wine producers were Italy (44.5 MhL), Spain (35.0 MhL), France (34.2 MhL), Germany (8.8 MhL), and Portugal (6.5 MhL) [13]. In 2021, the weather conditions did not favour grape growers in the European Union (EU), and wine production was estimated at 145 MhL (excluding juices and musts). Portugal, Germany, Romania, and Hungary were the only EU countries that recorded harvests greater than 2020 [13]. On average, about 30% of the grapes used for wine production become by-products, making this sector a good source of natural bioactive compounds [3,16,17,18,19]. These by-products are composed of vitamins, phenolic compounds (tannins, phenolic acids, anthocyanins, and resveratrol), water, proteins, lipids, carbohydrates, minerals, and compounds such as fiber [20]. Their concentration depends on the type of cultivars and climatic conditions of cultivation [21,22,23,24]. Some of these compounds present biological activities, such as antioxidant properties, and can be used in the food, pharmaceutical, and cosmetics industries [25,26,27]. In addition, several scientific studies are demonstrating the influence of bioactive compounds extracted from wine processing by-products on various diseases. [PERSON] et al. [28] reported that the bioactive compounds from grape stem had an anti-carcinogenic effect against colon, breast, and kidney cancers. Researchers have discovered valuable compounds in grape stems that possess strong antioxidant properties and antimicrobial abilities [29]. [PERSON] [30] analyzed grape pomace, which was of interest because the use of trans-resveratrol is associated with its anti-inflammatory and anticancer activities and cardioprotective, neuroprotective, and antioxidant effects.