Ferroptosis is a new type of cell death, which involves central neuronal system. Inhibition of ferroptosis is a promising strategy to prevent and treat neurological diseases. Thirteen phloroglucinols (1?13) were obtained from the whole plants of Hypericum japonicum. Of them, compounds 1–3 are new ones. Their structures were elucidated by extensive analysis of spectroscopic data and X-ray diffraction. All the isolates were evaluated for their inhibitory effect on RSL3-induced ferroptosis. Two new compounds 2–3 showed significant inhibitory effect with EC₅₀ of 0.48?±?0.14?μM and 0.94?±?0.14?μM, respectively. DPPH free radical scavenging abilities of all compounds were assessed to evaluate their antioxidant effect. This work first reports the anti-ferroptosis activity of phloroglucinols.