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Hericium erinaceus (Bull.) Persoon, a popular medicinal edible mushroom, owns a long history of usage in traditional Chinese medicine and also in other oriental countries. Along with this, its several bioactive compounds have been evolved into food supplements. Meanwhile, this present investigation aimed at extracting bioactive components from fruiting bodies of H. erinaceus using two different solvents and evaluating its in vitro antioxidant, antimicrobial, and antiproliferative efficacy. Chemical analysis showed extracts were rich in phenol, flavonoids, and ascorbic acids while lesser amount of carotenoids were also detected in these extracts. Both extracts were able to scavenge 1,1‐diphenyl‐2‐picrylhydrazyl (~76%) and 2,2′‐azinobis‐(3‐ethylbenzthiazoline‐6‐sulphonate) radicals (~81%) and also showed chelating activity (~73.05%). The ethanolic extract exhibited the highest antioxidant activity (total antioxidant capacity 2.17 µg ascorbic acid equivalent/mg of extract) whereas methanolic extract showed moderate capacity (total antioxidant capacity 1.42 µg ascorbic acid equivalent/mg of extract). All extracts displayed antibacterial activity against both Gram‐positive and Gram‐negative bacteria as well (minimum inhibition concentration 1,575–2,750 µg/ml) although methanolic extract showed some selectivity towards bacterial strains. Apart from these, ethanolic fraction has found to exhibit potent cytotoxicity (IC50 403.12 µg/ml) towards lung adenocarcinoma cells. These studies thus provide the reference data that could support this mushroom as an easily accessible source of natural bioactive components. Practical applications: Mushroom extracts have long been traditionally used as miracle medicine to treat an extensive range of ailments. These findings indicate the potential benefits of the Hericium erinaceus (Bull.) Persoon extracts for the development of multi‐target therapeutics as well as extraction with appropriate solvents also provide leads for the isolation of various principle compounds. The extracts thus could be used to treat oxidative stress‐related disorders as they are found to contain antioxidant compounds like phenols and others and also they possessed good antimicrobial and anticancer activity. [ABSTRACT FROM AUTHOR]