Brewer’s spent grain (BSG) is a residue that holds significant potential for various applications. Given its inherently high moisture levels, it becomes imperative to explore methods for preserving it. This study investigates the use of refractance window (RW) for drying BSG. The final moisture content, water activity, and drying kinetics were assessed. Various kinetic models were analyzed, including Lewis, Page, Overhults, Brooker, and Midilli. Employing a central composite design, this study also investigated the effects of the variables temperature (55.9 to 84.1 °C) and drying time (1.6 to 4.4 h) on the quality of the dried product. The quality was assessed based on the content of bioactive compounds: phenolics, flavonoids, citric acid, and ascorbic acid. The results suggest that refractance window (RW) drying can yield a product with reduced moisture content and water activity levels (lower than 10.0% and 0.600, respectively). The phenolic, flavonoid, and citric acid higher contents were found at 70 °C and 3 to 4 h of drying. The best ascorbic acid results were found at 55 to 65 °C after 3 h of drying. The use of RW emerges as an interesting alternative for processing BSG, offering a sustainable approach to better utilize this residue.