Synedrella nodiflora (L.) Gaertn. (Asteraceae), is a weed with ethnomedicinal uses. To extend scientific information on this species, we evaluated the effects of different extraction procedures (maceration, Soxhlet, sonication and homogenizer-assisted extraction (HAE)) using methanol as solvent, on the chemical composition and biological potential. The chemical profiles of the extracts were identified using a chromatographic (UHPLCHRMS) technique. The antioxidant and enzyme inhibitory activities of the studied extracts were determined. The extract obtained by Soxhlet technique showed a higher level of total phenolic (TPC) and flavonoid content (TFC) and was a superior source of antioxidant compounds. The macerated extract was the most potent inhibitor of cholinesterases and alpha-glucosidase, whereas the highest activity against tyrosinase was observed in the order of sonication > Soxhlet > HAE > maceration. A modest activity was observed against a-amylase for all the extracts. Multivariate analysis showed that the bioactive compounds recovery and the biological activities of S. nodiflora were mostly dependent on the nature of the extraction technique used. In conclusion, S. nodiflora extracts showed good biological potential and data massed from this study could serve as a scientific baseline for further investigation in order to exploit its potential for designing novel bio-products with therapeutic applications.