A broad set of potential bioactive conjugate compounds has been semi-synthesized through solution- and solid-phase organic procedures, coupling two natural pentacyclic triterpene acids, oleanolic (OA) and maslinic acids (MA), at the hydroxyl groups of the A-ring of the triterpene skeleton, with 10 different acyl groups. These acyl OA and MA derivatives have been tested for their anti-proliferative (against the b16f10 murine melanoma cancer cells) and antiviral (as inhibitors of the HIV-1-protease) effects. Several derivatives have shown high levels of early and total apoptosis (up to 90%). Most of the compounds that exhibited anti-proliferative effects also generated ROS, probably involving the activation of an intrinsic apoptotic route. The only four compounds that did not cause the release of ROS could be related to the participation of a probable extrinsic activation of the apoptosis mechanism. A great number of these acyl OA and MA derivatives have proved to be potent inhibitors of the HIV-1-protease, the most active inhibitors having IC50 values between 0.31 and 15.6 μM, these values being between 4 and 186 times lower than their non-acylated precursors. The potent activities exhibited in the apoptosis-activation processes and in the inhibition of the HIV-1-protease by some OA and MA acylated derivatives imply that these compounds could be used as new, safe, and effective anticancer and/or antiviral drugs.