<p><i>Fagonia glutinosa</i> has been traditionally used by Saharan populations in Algeria for its therapeutic properties. The present investigation was designed to identify the plant’s bioactive constituents and to evaluate its in vitro antioxidant, antiarthritic, and antimicrobial activities, as well as its in vivo antipyretic and anti-hemorrhoidal effects. The aerial parts of <i>F. glutinosa</i> were extracted with petroleum ether, ethyl acetate, and <i>n</i>-butanol, and the two last fractions were analyzed using HPLC–DAD/MS. The antioxidant potential of these extracts was assessed using four assays namely DPPH, ABTS, SNV, and PRAC. Antiarthritic activity was determined through the inhibition of bovine serum albumin (BSA) denaturation, whereas antimicrobial testing was carried out against selected bacterial and fungal strains. Antipyretic activity was investigated in rats using the yeast-induced pyrexia model. In addition, the anti-hemorrhoidal potential was assessed in croton oil–induced hemorrhoid rats. Investigation of the phytochemical profile from <i>F. glutinosa</i> revealed the presence of functionally important polyphenols. Indeed, seven flavonoids were reported for the first time from <i>F. glutinosa</i>. Also, tricoumaroyl spermidine (coumarin) was identified, for the first time in this plant, and quantified as the most abundant phenolic compound. Biologically, the plant fractions exhibited strong antioxidant capacity, pronounced antiarthritic activity. In vivo studies with rat models confirmed a dose-dependent antipyretic effect, as well as notable anti-hemorrhoidal activity. The results reinforce the traditional use of <i>F. glutinosa</i>, demonstrating that its bioactive constituents may serve as effective agents for alleviating fever, hemorrhoids, and inflammatory disorders, thereby supporting its potential as a natural therapeutic alternative.</p> Graphical abstract <p></p>