The approach developed here offers a straightforward and efficient access to -C-glycosyl barbiturates ligands, spanning from glycomimetics to multivalent C-neoglycoconjugates, with the aim of deciphering structural parameters impacting the binding to pathogenic lectins. We reinvestigated the Knoevenagel condensation of barbituratic acid on protecting-group free carbohydrates and successfully designed sodium and 5,5-disubstituted N,N-dimethyl barbiturate forms of D-galactose, Lfucose, melibiose, 2'-fucosyllactose, maltose and evaluated their binding affinity by isothermal titration calorimetry with LecA (galactose-binding lectin) and LecB (fucose-binding lectin) from Pseudomonas aeruginosa and RSL (fucose-binding lectin) from Ralstonia solanacearum. The barbiturate ring was shown detrimental for binding to LecA (K D in mM range) and even more to LecB (non-interaction) while RSL is much more tolerant especially in presence of an aromatic group (K D in M range). However, distancing the barbiturate ring from the recognition carbohydrate residue by using oligosaccharides increased affinity up to low micromolar range. Extension of our convenient synthetic approach led in two-steps to melibiose-based C-glycosyl barbiturates clusters and C-glycosyl barbiturate glycopolymers exhibiting a dramatic enhancement of binding avidity for LecA.