Carboxyl-containing compounds (CCCs) are indispensable for human body and related to the management of numerous diseases. However, it is still rather challenging to determine them in food both qualitatively and quantitatively because of their similar or diverse structures and the difference of polarity, concentration, ionization efficiency, and separation ability. Fortunately, derivatization-LC-MS can overcome such limitation and has been playing a more important role in food chemistry for recent decades. There have been no systematic reviews about CCCs together in food, thus CCCs were grouped and discussed comprehensively in terms of structures, biological functions, and abundant food sources. In addition, how derivatization LC-MS technique can provide increased detection sensitivity, improved chromatographic separation, improved identification capacity, and accurate quantitative capacity are summarized. Herein we aim to emphasize various functional CCCs in food and identify derivatization LC-MS as a powerful analytical tool to analyze food samples.