Pyropia haitanensis polysaccharides have attracted growing attention for their diverse biological activities. In this study, we developed a synergistic extraction approach combining ultrasonic-assisted treatment and enzymatic hydrolysis using cellulase and pectinase. Response surface methodology (RSM) was applied to optimize the extraction conditions, which were determined as follows: 1.48% cellulase, 1.47% pectinase, 180 W ultrasonic power, and 65.9 °C temperature. Under these conditions, the polysaccharide yield reached 10.184 ± 0.27%. The crude extract was then purified through sequential DEAE Sepharose FastFlow and Sephadex G-75 chromatography, resulting in the purified fraction PPHP3. Monosaccharide analysis revealed that galactose, glucose, and glucuronic acid constituted the primary components in a molar ratio of 98.3:0.46:1.24. This polysaccharide exhibited a weight-average molecular weight of 25.208 kDa, a sulfate content of 8.64 ± 0.05%. In hypolipidemic assays using oleic acid-induced HepG2 cells, PPHP3 significantly reduced intracellular triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), while simultaneously increasing HDL-C levels. These findings highlight the potential of P. haitanensis polysaccharides for hypolipidemic applications and establish a scientific foundation for their development in therapeutic and practical contexts.