The winemaking process generates by-products such as grape pomace (GP) and wine lees (WL) and wastes like wastewater (WW) and waste-activated sludge (WAS), which represent a significant source of organic matter potentially promising for biogas production. This study evaluates the anaerobic digestion (AD) performance of these winery by-products and wastes by determining their Biochemical Methane Potential (BMP) under mesophilic conditions. Direct (GP and WL) and indirect (WW and WAS) winery by-products were characterized for their physicochemical composition, and BMP tests were used to determine methane yields, biogas composition, and biodegradability. Tailored strategies were devised to enhance their BMP potential. Results demonstrated that fresh WL yielded minimal methane production. In contrast, samples stored at − 80 ℃ exhibited a marked increase in methane generation, likely attributable to an elevated concentration of soluble organic compounds. A comparable, albeit less pronounced, enhancement in methane production was observed for GP samples following − 80 ℃ storage. The composition of the indirect by-products (WW and WAS) is highly influenced by seasonal variations, which in turn impacts their suitability for industrial-scale applications. Co-digestion of these substrates emerges as a promising strategy to overcome such limitations by maximizing synergistic interactions and optimizing biodegradability.