A library of novel sulfanyl, sulfinyl, and sulfonyl group-containing ursane conjugates with 1,3,4-oxadiazoles and 1,2,4-triazoles were designed and obtained. The target compounds were synthesized by alkylation of the corresponding azole-based thiones followed by S-selective oxidation. The expected sulfoxides and sulfones were obtained depending on the applied excess of mCPBA without oxidation of the ursane double bond. The novel products were studied for their antiproliferative activity on cell lines MCF7 (breast cancer), U-87 MG (glioblastoma multiform cells), A549 (lung carcinoma), and U-87 MG (hepatocarcinoma), using immortalized human fibroblasts hTERT as non-cancer control. Oxadiazole-derived methylsulfones possessed the most notable cytotoxicity, while the sulfanyl group containing ursane conjugates with 1,2,4-triazoles 7 g, 7 h exhibited the best selectivity and antiproliferative activity, superior to ursolic acid and starting azole-based thiones. Possible mechanism of action of thioethers 7 g, 7 h was studied using molecular modeling.