The influence of a 2.5% and 5% addition of dried Reishi and Lion’s Mane mushrooms on the content of bioactive compounds and some pro-health properties of pasta was studied. In samples subjected to gastrointestinal digestion, the content of phenolic compounds and the antioxidant, potential anti-inflammatory, and antiproliferative properties were significantly higher. The qualitative–quantitative analysis of phenolic compounds performed using the LC-MS/MS technique indicated that the Reishi-enriched pasta was characterized by a higher content of syringic (R2.5 sample), while pasta supplemented with Lion’ Mane had a higher content of vanillin in relation to the control pasta. In the case of ethanolic extracts, samples supplemented with the Reishi mushrooms (R5 sample) were characterized by higher ABTS antiradical properties and a reducing power while the sample supplemented with Lion’s Mane (L5 sample) had a higher ability to inhibit lipoxygenase in relation to the control sample. In conclusion, the results suggest that Reishi and Lion’s Mane mushroom powder can be used for the fortification of semolina pasta, conferring slightly healthier characteristics of the product.