Fifteen epi-aleuritolic acid derivatives were synthesized and evaluated for anti-HIV activity in 293 T cells and NO production inhibition activity. Of the derivatives, 1, 2, 3, 4, 11, and 13 showed relatively potent anti-HIV activity with EC50 values ranging from 5.80 to 13.30 μM. The most potent compound, 3α-2',2'-dimethylsuccinic acyl epi-aleuritolic acid (11), displayed significant anti-HIV activity with an EC50 value of 5.80 μM. Compounds 1, 3, 4, and 11 showed NO inhibition activity, with IC50 values ranging from 3.40 to 7.10 μM and compound 1 inhibited NO production with an IC50 value of 3.40 μM.