Drug screening is crucial in drug development; animal models serve as an essential foundation for disease research and screening. The selection of suitable models can elucidate disease mechanisms, reduce research costs, and expedite research. Caenorhabditis elegans ( C. elegans ), a multicellular eukaryote, has become an invaluable tool in life sciences research because of its minimal ethical concerns, short life cycle, low cost, ease of experimental manipulation, fully sequenced genome, and significant homology with the human genome. This article synthesizes recent literature to review the progress in drug screening using C. elegans, including its application in aging, age-related neurodegenerative disease, anti-tumor, and anti-infection models; additionally, effective drugs screened with these models are summarized, aiming to provide theoretical references and foundations for future research.