Caenorhabditis elegans (C. elegans) is a powerful model organism which has been extensively characterized at the genetic and cellular levels and used to study various biological processes. However, less is known about how metabolic pathways operate in C. elegans and how metabolites participate in worm's physiology. Metabolomics and lipidomics have emerged as valuable tools for understanding C. elegans biology and its association with physiological and pathological conditions in humans. Metabolomics and lipidomics methods are diverse and lead to different outcomes depending on a number of variables, including sample preparation, metabolite extraction, the method of detection and data analysis. In this Review, the main steps involved in C. elegans lipidomics and metabolomics analyses are presented, directing particular attention to the advantages and drawbacks of each method of sample preparation and processing in terms of simplicity and metabolite coverage, and also listing the most frequently used protocols and their applications.