The Guardians of Guthix are a group of creatures chosen by Guthix himself, who were his trusted and empowered companions while he walked the world at the end of the Third Age. As he headed to sleep, he assigned some guardians to guard important locations (in the case of Fiara (Fist of Guthix)) or philosophies (in the case of Death) of the Guthixian religion at the end of the Third Age. According to Mod Osborne, there were originally as many Guardians as standing stones in a druids' circle, totalling eight. Some of the Guardians are blessed with great power and/or wisdom on Gielinor, greater even than some low-tier gods and divine beings.
- Juna - Guardian of the Tears of Guthix - Juna is the guardian of the Tears of Guthix cave, an underground spring where Guthix wept for those lost in the God Wars.
- Death (NPC) - Harold Death Esq., or the Grim Reaper, is tasked to regulate life in order to reach balance. He controls the process of respawning and has the ability to expand or shorten the lifespan of mortals in order to prevent or provide death, provided that individual's time has come. Per his role as a Guardian, he cannot randomly commit murders if their time hasn't come; likewise, he cannot save a life if their time has come, as much as he or they may wish it, or revive the dead.