Growing insights into the functionality of lectin–carbohydrate interactions are identifying attractive new targets for drug design. As glycan recognition is regulated by the structure of the sugar epitope and also by topological aspects of its presentation, a suitable arrangement of ligands in synthetic glycoclusters has the potential to enhance their avidity and selectivity. If adequately realized, such compounds might find medical applications. This is why we focused on lectins of clinical interest, acting either as a potent biohazard (a toxin from Viscum album L. akin to ricin) or as a factor in tumor progression (human galectins-1, -3, and -4). Using a set of 14 calix[n]arenes (n=4, 6, and 8) with thiourea-linked galactose or lactose moieties, we first ascertained the lectin-binding properties of the derivatized sugar head groups conjugated to the synthetic macrocycles. Despite their high degree of flexibility, the calix[6,8]arenes proved especially effective for the plant AB-toxin, in the solid-phase model system with a single glycoprotein (asialofetuin) and with human tumor cells in vitro. The bioactivity of the calix[n]arenes was also proven for human galectins. Notably, selectivity for the tested tandem-repeat-type galectin-4 among the three subgroups was determined at the level of solid-phase and cell assays, the large flexible macrocycles again figuring prominently as inhibitors. Alternate and cone versions of calixarene with lactose units distinguished between galectins-1 and -4 versus galectin-3 in cell assays. The results thus revealed bioactivity of galactose-/lactose-presenting calix[n]arenes for medically relevant lectins and selectivity within the family of adhesion/growth-regulatory human galectins.