New 1,3,4-thiadiazole thioglycosides linked to substituted arylidine systems were synthesized via glycosylation of the prepared 1,3,4-thiadiazole thiol compounds. Click strategy was also used for the synthesis of new 1,3,4-thiadiazole and 1,2,3-triazole hybrid glycosides by reaction of the acetylenic derivatives with different glycosyl azids followed by deacetylation process. The cytotoxic activities of the prepared compounds were studied against HCT-116 (human colorectal carcinoma) and MCF-7 (human breast adenocarcinoma) cell lines using the MTT assay. The results showed that the key thiadiazolethione compounds and , the triazole glycosides linked to -methoxyarylidine derivatives and in addition to the free hydroxyl glycoside were found potent in activity comparable to the reference drug doxorubicin against MCF-7 human cancer cells. The acetylenic derivative and glycoside were also found highly active against HCT-116 cell lines.