Lapachol (1), a natural naphthoquinone, presents several biological activities including antitumor activity, used as anticancer coadjuvant whose use was abandoned because of adverse effects. Herein, we reported the synthesis and cytotoxicity evaluation against cancer cell lines of a series of Oglycosides and glycosyl triazoles derived from lapachol. In addition to the determination of IC50, the DNA fragmentation and clonogenicity were also evaluated. The glycoside derived from D-glucose (5) was far more active than lapachol (1) and more active in tumor cell lines HL60, Jurkat, THP-1 and MDA-MB-231 than to the non-tumoral PBMC cell line, indicating an improvement in activity and selectivity as compared with lapachol (1). Compound 5 and the glycosides derived from D-galactose (14), D-N-acetylglucosamine (15) and L-fucose (16) showed good results in the DNA fragmentation and clonogenicity assays in the studies of subdiploid DNA content, indicating a pro-apoptotic potential and a good antiproliferative activity of these glycosides.