Sphagneticola calendulacea (L.) Pruski, belonging to the Asteraceae family, has been traditionally used in various Asian countries to treat a range of illnesses. This research aimed to compare the phenolic composition, antioxidant activity, and inhibitory effects of S. calendulacea leaf extracts on α-amylase, xanthine oxidase, and albumin denaturation obtained using conventional solvent, ultrasonic, and enzyme-assisted extraction methods. The ultrasonic extraction method yielded higher levels of phenolics and demonstrated a stronger free radical scavenging activity (IC50 = 53.31 ± 4.68 μg/mL) compared to the other methods. The enzyme-assisted extraction produced the extract with higher potent inhibitory effects on α-amylase (IC50 = 769.33 ± 75.52 μg/mL) and albumin denaturation (259.91 ± 9.85 μg/mL). The ethanolic extract exhibited the strongest inhibition of xanthine oxidase (IC50 = 153.35 ± 25.99 μg/mL) among the extracts. Based on the results, ultrasonic extraction is suggested as the optimal approach for obtaining phenolic-rich extracts with strong antioxidant potential, while enzyme-assisted extraction may be preferable for specific inhibitory activities. These findings enhance our understanding of the bioactive phenolics and potential health-promoting benefits associated with S. calendulacea leaves.
