Beer production produces significant amounts of brewers’ spent grain (BSG), a lignocellulosic by-product with important environmental and economic impacts. Despite its high moisture content and rapid microbial breakdown, BSG has a stable, nutrient-rich composition, especially high in protein, fiber, and polyphenolic compounds. While its perishability limits direct use in food systems, BSG is often repurposed as livestock feed. Recent advances in bioprocessing and extraction technologies have expanded their use across different sectors. This review explores the composition of crude BSG and evaluates innovative valorization methods, including recovering bioactive compounds with pharmaceutical and nutraceutical value, and converting them into biofuels such as biogas, biodiesel, and bioethanol. Special focus is given to methods involving enzymatic hydrolysis, fermentation, and chemical extraction to isolate proteins, peptides, amino acids, sugars, and polyphenols. By analyzing emerging applications and industrial scalability challenges, this review highlights BSG’s growing role within circular economy models and its potential to promote sustainable innovations in both the brewing industry and the wider bioeconomy.