Nematode parasites cause substantial morbidity to billions of people and considerable losses in livestock and food crops. The repertoire of effective anthelmintic compounds for treating these parasitoses is very limited, as drug development has been delayed for decades. Moreover, resistance has become a global concern in livestock parasites and is an emerging issue for human helminthiasis. Therefore, anthelmintics with novel mechanisms of action are urgently needed. Taking advantage of Caenorhabditis elegans as an established model system, we here screened the nematicidal potential of novel imidazolium and imidazole derivatives. One of these derivatives, diisopropylphenyl-imidazole (DII), is lethal to C. elegans at both mature and immature stages. This lethal effect appears to be specific because DII concentrations which prove to be toxic to C. elegans do not induce significant lethality on bacteria, Drosophila melanogaster, and HEK-293 cells. Our analysis of DII action on C. elegans mutant strains determined that, in the adult stage, null mutants of unc-29 are resistant to the drug. Muscle expression of this gene completely restores DII sensitivity. UNC-29 has been largely reported as an essential constituent of the levamisole-sensitive muscle nicotinic receptor (L-AChR). Nevertheless, null mutants in unc-63 and lev-8 (essential and non-essential subunits of L-AChRs, respectively) are as sensitive to DII as the wild-type strain. Therefore, our results suggest that DII effects on adult nematodes rely on a previously unidentified UNC-29-containing muscle AChR, different from the classical L-AChR. Interestingly, DII targets appear to be different between larvae and adults, as unc-29 null mutant larvae are sensitive to the drug. The existence of more than one target could delay resistance development. Its lethality on C. elegans, its harmlessness in non-nematode species and its novel and dual mechanism of action make DII a promising candidate compound for anthelmintic therapy. Intestinal helminth infections affect approximately one-third of the world’s population, particularly in developing countries. Paradoxically, drug development in this area has been delayed for years. In addition, resistance to currently available drugs is also an emerging global concern. Therefore, there is an urgent need for new and effective anthelmintics. In this work, we used C. elegans as a model for parasitic nematodes to screen the anthelmintic activity of several imidazole-derivative compounds. We found a compound, diisopropylphenyl-imidazole (DII), that is lethal to both mature and immature stages of C. elegans. The DII nematicidal mechanism of action depends on a novel UNC-29-containing AChR in adult C. elegans muscle. Since this mechanism is different from those of currently used anthelmintics, it could constitute a therapeutic option when traditional anthelmintic agents fail. In addition, we found that the DII larvicidal effect depends on a different target to that of adult stages. The fact that DII produces lethality through different targets may delay resistance development. The specificity and novel mode of action of DII, which includes differential targeting in larvae and adult nematodes, support its potential as a promising drug candidate to treat helminthiasis.