Mushrooms stand out as one of nature's best gifts among the natural product sources with their diversity, therapeutic values and increasing popularity. In this study, antioxidant (ABTS·+ scavenging, β-carotene-bleaching, cupric-reducing antioxidant capacity (CUPRAC), DPPH· scavenging, and metal chelating assays), and enzyme (buty-rylcholinesterase (BChE) and acetylcholinesterase (AChE), α-amylase and α-glucosidase) inhibition activities of the extracts obtained from Coprinus comatus (O.F. Müll.) Pers., Cerrena unicolor (Bull.) Murrill, Inocutis rheades (Pers.) Fiasson & Niemela and Leptoporus mollis (Pers.) Quél. mushroom species were investigated. The presence of phenolic and organic acid compounds associated with the bioactive properties of the mushroom species was determined by HPLC-DAD. Fumaric acid was found to be prominent compound in C. comatus (43.90 µg/g dw) and C. unicolor (659.9 µg/g dw), vanillin in L. mollis (19.48 µg/g dw), and p-coumaric acid in I. rheades (21.32 µg/g dw). L. mollis methanol extract, as well as higher antioxidant activity than the standards in CUPRAC and β-carotene-bleaching assays, was noted as superior antioxidant active in all assays (except metal chelating). C. comatus possessed the highest inhibition activity on α-amylase (IC50: 0.23 mg/mL for methanol extract), AChE (IC50: 125.50 µg/mL for hexane extract), and BChE (IC50: 61.03 µg/mL for methanol extract). Also, C. comatus methanol (IC50: 0.09 mg/mL) and L. mollis hexane (IC50 : 0.11 mg/ mL) extracts were better α-glucosidase inhibition active than the acarbose (IC50: 0.37 mg/mL). Our study ascertained that the studied mushroom species are particularly sources of biochemically active compounds with therapeutic potential.