Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons, for which there is no effective treatment. Previously, we generated a Caenorhabditis elegans model of ALS, in which the expression of dnc-1, the homologous gene of human dynactin-1, is knocked down (KD) specifically in motor neurons. This dnc-1 KD model showed progressive motor defects together with axonal and neuronal degeneration, as observed in ALS patients. In the present study, we established a behavior-based, automated, and quantitative drug screening system using this dnc-1 KD model together with Multi-Worm Tracker (MWT), and tested whether 38 candidate neuroprotective compounds could improve the mobility of the dnc-1 KD animals. We found that 12 compounds, including riluzole, which is an approved medication for ALS patients, ameliorated the phenotype of the dnc-1 KD animals. Nifedipine, a calcium channel blocker, most robustly ameliorated the motor deficits as well as axonal degeneration of dnc-1 KD animals. Nifedipine also ameliorated the motor defects of other motor neuronal degeneration models of C. elegans, including dnc-1 mutants and human TAR DNA-binding protein of 43 kDa overexpressing worms. Our results indicate that dnc-1 KD in C. elegans is a useful model for the screening of drugs against motor neuron degeneration, and that MWT is a powerful tool for the behavior-based screening of drugs.