Spent coffee ground (SCG) represent a food waste with functional potential, produced in high amount worldwide. SCG derive from coffee brewing and are mainly composed of insoluble matter and different efforts is still necessary to find innovative processes for their valorization. In this work, different methodologies including physical (cryogenic milling and microwave assisted extraction, MAE) and biological (optimized enzyme-assisted extraction, EAE) were exploited to solubilize compounds trapped within the abundant fiber network. MAE led to the highest concentration of soluble fiber and oligosaccharides thus solubilizing insoluble fiber. The total soluble matter increased almost 8 folds by using MAE and EAE in combination due to high insoluble fiber hydrolysis into monosaccharides (up to 17 g/100g), soluble melanoidins (up to 72 mg/g) and caffeic acid (up to 2.22 mg/g). The extract was also characterized for the highest antioxidant potential demonstrating the positive impact of combined process. The EAE promoted the release of nutrients in SCG extract which were used as a growth substate by the selected probiotic Lactiplantibacillus plantarum LP19. This work demonstrates how different technologies and their combination can be used to valorize SCG demonstrating the possibility to obtain novel SCG-derived functional ingredients and/or products.