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Two new xanthones (<b>1</b> and <b>2</b>) were isolated from the deep-sea-derived fungus <i>Penicillium</i> sp. MCCC 3A00126 along with 34 known compounds (<b>3</b>–<b>36</b>). The structures of the new compounds were established by spectroscopic data. The absolute configuration of <b>1</b> was validated by comparison of experimental and calculated ECD spectra. All isolated compounds were evaluated for cytotoxicity and ferroptosis inhibitory activities. Compounds <b>14</b> and <b>15</b> exerted potent cytotoxicity against CCRF-CEM cells, with IC₅₀ values of 5.5 and 3.5 μM, respectively, whereas <b>26</b>, <b>28</b>, <b>33</b>, and <b>34</b> significantly inhibited RSL3-induced ferroptosis, with EC₅₀ values of 11.6, 7.2, 11.8, and 2.2 μM, respectively.