This study investigates two extraction methods-ultrasound-assisted extraction (UAE) and compound enzyme extraction (CE)-for the isolation of Lonicera macranthoides polysaccharides (LMP) and evaluates their physicochemical properties, bioactivity, and therapeutic potential. The optimization of extraction conditions was performed using single-factor experiments and response surface methodology. The yield of LMP from UAE was optimized to 8.02 % ± 0.12 %, while the yield from CE was 10.03 % ± 0.32 %. Both polysaccharide extracts were characterized in terms of chemical composition, monosaccharide composition, molecular weight, thermal stability, and functional group analysis. Notably, UAE-LMP exhibited superior antioxidant, hypolipidemic, nitrite scavenging, and anti-tumor activities compared to CE-LMP. The ultrasound-assisted method enhanced the stability and bioactivity of LMP, with improved water- and oil-holding capacities and the integrity of the active groups. Our findings demonstrate that the extraction method significantly influences the structural and functional properties of LMP, suggesting that UAE may be a more effective approach for extracting bioactive polysaccharides with potential applications in medicine and nutrition.