The application of solid-state fermentation for the production of value-added products from the agro- and food-industry residues has been recently investigated greatly. The white-rot basidiomycete Trametes versicolor is a widely used fungi for the degradation lignocellulosic material in solid-state conditions. Grape pomace constitutes the major by-product of Vitis vinifera L. and is a source of compounds with recognized health benefits. In this study, a process for treating grape pomace with Trametes versicolor for 15 days under solid-state conditions was developed, and the phenolic profile and anti-inflammatory potential of the grape pomace extracts before and after treatment was studied. The anti-inflammatory potential of the grape pomace extracts was studied via tests based on the inhibition of 5-lipoxygenase and hyaluronidase, two key enzymes in inflammatory processes. A total of 24 phenolic compounds were identified and quantified by HPLC methods. With the exception of anthocyanins, an increase in phenolic acids, flavan-3-ols and the flavonol rutin was observed after a treatment period of 1-4 days with T. versicolor. Moreover, the increase in the phenolic content was accompanied by an enhancement in the anti-inflammatory activity of the grape pomace extracts, which was confirmed by the strong correlation between them. This is the first study providing evidence of the benefits of the application of fungal-based solid-state fermentation as an environmentally friendly process for the enhancement of the phenolic composition and anti-inflammatory potential of grape pomace, increasing the possibility of profiting from the great waste produced by the grape-processing industry.