Coffee husk is a fibrous mucilaginous material representing the major residues from the handling and processing of coffee. Currently, coffee husk is discarded which contributes to environmental pollution. Dry and semi-dry coffee husk were extracted by hot infusion and the polyphenol profile was studied by UHPLC and Q-Orbitrap mass spectrometry. Free radical scavenging activity in the infusion was between 26.61 at 31.33 mmol Trolox equivalent antioxidant capacity (TEAC)/kg, as measured by the assay with ABTS and DPPH radical. The results indicated that coffee husk contained 367.45 and 396.04 g/kg of total dietary fiber in dry and semi-dry sample, respectively. While the infusions contain exclusively soluble dietary fiber 0.64 and 0.98 g/L. The methanol extracts of coffee husk presented antimicrobial activity of P. camemberti, P. expansum and P. roqueforti, A. flavus and A. niger, many of their mycotoxins producers. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values for the Penicilliums strains ranged from 6.3 to 50 g/L, whereas on the Aspergillus strains the data detected ranged from 25 to 50 g/L, respectively. This study indicates the possible exploiting of this coffee by-product as potential natural health promoting and preservative ingredient.