Chemical investigation of the aerial parts of Pentzia monodiana Maire led to the isolation and identification of one sesquiterpene lactone glucoside of the guaianolide type (dihydropseudoivalin-4-O-β-d-glucopyranoside), along with nine known compounds including one diterpenoid, two sesquiterpenoids, three lignanes and three flavonoids. Their structures were established on the basis of spectroscopic analysis. All these compounds were evaluated for their DPPH radical scavenging and tyrosinase inhibitory activities. Only lignanes and flavonoids showed good to moderate DPPH radical scavenging activity with EC50 ranging from 10.6 to 47.5 μM. The new sesquiterpene lactone glucoside showed low tyrosinase inhibitory activity whereas the isolated lignanes and flavonoids exhibited a moderate activity with IC50 ranging from 45.4 to 97.2 μM).