Four new compounds including two eremophilane sesquiterpenes, penicilleremophilanes A (1) and B (2), as well as two sulfur-containing biphenols, penicillithiophenols A (3) and B (4), were isolated from the soil fungus Penicillium copticola PSU-RSPG138 together with 16 known compounds. Their structures were elucidated by spectroscopic methods. Known sporogen AO-1 exhibited significant antimalarial activity against Plasmodium falciparum with an IC50 value of 1.53 μM and cytotoxic activity to noncancerous (Vero) cell lines with an IC50 value of 4.23 μM. Although compound 1 was approximately half as active against P. falciparum with the IC50 value of 3.45 μM, it showed much weaker cytotoxic activity.