Mangiferin is a xanthonoid found in Mango leaves in abundance with many effects as a hypoglycemic, antioxidant, and anti-inflammatory agent, plant metabolite, and so on. However, nowadays, mango leaves are merely a waste product in Vietnam. To take advantage of this valuable medicinal resource, extraction conditions of mangiferin using classical and ultrasound methods were researched, and mangiferin was purified from Cat Chu mango leaves (Mangifera indica L., Anacardiaceae) collected in Dong Thap. Ultrasound-assisted extraction method was conducted with the following conditions and mangiferin was extracted at a percentage of 6.728% with a purity of 91.11%. Purified mangiferin was evaluated using molecular absorption spectroscopy UV-Vis, scanning electron microscopy (SEM), X-ray diffraction (XRD) spectroscopy, simultaneous thermal analysis (STA: TGA/DSC), and dissolution measurement method. To optimize the solubility and permeability of mangiferin, the solid dispersion system (HPTR) was made by the combination of HPMC 6M:mangiferin at the ratio of 1:5. To investigate the acute, sub-chronic toxicity and hypolipidemia effect of HPTR as compared to purified mangiferin, we followed guidelines for preclinical and clinical trials of Traditional Medicine and Herbal Medicines by the Vietnam Ministry of Health and OECD, and used tyloxapol (Triton WR1339, 400 mg/kg, i.p.) to induce hyperlipidemia. Our results indicated that purified mangiferin and HPTR extract showed no acute toxicity and sub-chronic toxicity and has potential as an antihyperlipidemic agent. The HPTR brought about a significant decrease in total cholesterol, triglycerides and LDL-c when compared to mangiferin, however there was no significance between them.