AbstractIn this study, we report the use of a 1,8‐diazabicyclo [5.4.0]‐undec‐7‐en‐8‐ium imidazolate ionic liquid as a catalyst as well as a green solvent for the expeditious multicomponent transformation of tetra‐ and trisubstituted imidazole scaffolds via four‐ and pseudo‐four‐component reactions with short reaction time, excellent yield, and purity of products. The ionic liquid is cheap, biodegradable, and can be recovered and reused for more than five consecutive cycles. The advantage of this protocol for gram‐scale synthesis adds to its practical applicability. Selected synthesized tetra‐ and trisubstituted imidazole scaffolds were screened for their in vitro antiproliferative properties against the human cancer cell lines EC‐109, MCF‐7, HGC‐27, and PC‐3. Compounds 4m, 5e, and 5v showed potent cytotoxic activity against the human breast cancer cell line PC‐3, MCF‐7, and HGC‐27, respectively.