Amphiphilicity is one of the desirable features in the process of drug development which improves the biological as well as the pharmacokinetics profile of bioactive molecule. Carbohydrate moieties present in anti-cancer natural products and synthetic molecules influence the amphiphilicity and hence their bioactivity. This review focuses on natural and synthetic amphiphilic anti-cancer glycoconjugates. Different classes of molecules with varying degree of amphiphilicity are covered with discussions on their structure-activity relationship and mechanism of action.