Helichrysum stoechas (L.) Moench is one of the scientific names of everlasting flower, which has traditionally been used as an ornamental, medicinal and food plant. The aim of this study was to identify the main phytochemical constituents as well as to evaluate the potential of this plant in terms of antioxidant, antidiabetic and neuroprotective activities. The phytochemical analysis of the methanolic extract allowed for the identification of ten constituents mainly of phenolic nature and with chemosystematic relevance: two heterodimeric phloroglucinols, arzanol (1) and compound (3), one homodimeric α-pyrone, helipyrone (2), three phenolic acids, p-hydroxybenzoic (4), caffeic (5) and neochlorogenic (6) acids, one polymethoxylated and two glycosidic flavonoids, 5,7-dihydroxy-3,6,8-trimethoxyflavone (7), isoquercitrin (8) and quercetagetin-7-O-glucopyranoside (9) together with santinol B (10). Bioassays showed significant antioxidant and antiproliferative effects and for the first time the potential of Helichrysum stoechas to inhibit the MAO-A, AChE and TYR enzymes, as well as to exert anti-α-glucosidase and anti-dipeptidyl peptidase-4 activities.