Foeniculum vulgare is a perennial aromatic plant whose cultivation produces large amounts of waste rich in bioactive compounds with promising anti-inflammatory activities. Nine selected metabolites were quantified through Ultra Performance Liquid Chromatography (UPLC) hyphenated to QTRAP mass spectrometry by using MRM (multiple reaction monitoring) was performed on four parts of fennel: bulb, stem, little stem, and leaf. Analysis revealed significant differences in the amount of quantified metabolites, suggesting that little stem and leaf are the most valuable parts of the waste. Phenolic acids and glycosylated flavonoids were quantified for their known possible anti-inflammatory activities; in fact, due to this reason their ability to inhibit COX-1 and COX-2 isoforms was evaluated through a fluorometric assay, resulting in specific inhibitors of COX-2 at certain concentrations. In conclusion, as the leaf of fennel may be beneficial to human health, clinical studies should include it in nutraceuticals or functional foods for human consumption.