Brewer’s spent grain (BSG) is a widely recognized byproduct of beer production that retains valuable nutritional components. Its upcycling promotes nutrient recovery from waste and minimizes the nutrient loss to the environment. The presence of antinutrient phytic acid (PA) in food and feed products is linked to decreased mineral and protein bioavailability due to the formation of insoluble complexes. The levels of PA can be effectively reduced through fermentation with microorganisms that produce phytase, which releases soluble forms of phosphorus that are more readily bioavailable. To enhance the nutritional quality of BSG, it was used as a substrate for solid-state fermentation (SSF) with the edible mushroom Pleurotus ostreatus, specifically targeting a reduction in the PA content and an increase in the phosphorus bioavailability. After 14 and 21 days of fermentation, we assessed the levels of PA, total phosphorus, and acid-soluble phosphorus. After 14 days of SSF, the PA content was reduced by 81%, resulting in a doubling of the soluble phosphorus content. Furthermore, the total phosphorus significantly increased at both time points. This study demonstrates that BSG can be effectively revalorized through SSF with P. ostreatus, significantly reducing the antinutrient PA content while enhancing the phosphorus content, particularly regarding its bioavailable form. These findings underscore the potential for upcycling food byproducts like BSG, contributing to sustainable practices and promoting resource efficiency in food systems.