The extraction of total flavonoids from Hylotelephium spectabile (Boreau) H. Ohba (H. spectabile) leaves was studied through the use of a double enzyme-assisted ultrasonic method, and the extraction process was optimized using the Box–Behnken design. Eight different macroporous resins were screened for purification in single-factorial experiments, and the flavonoid compounds in the extract of H. spectabile leaves were identified using HPLC-MS. Through the evaluation of the total reducing capacity and capacity for reducing 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH), hydroxyl radicals (·OH), and 2,2’-biazobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), the in vitro antioxidant activities of the crude extracts of the total flavonoids and purified total flavonoids of H. spectabile leaves were investigated. The results showed that the most efficient conditions for flavonoid extraction were an ultrasonic extraction time of 60 min, an ethanol concentration of 35%, a liquid-to-material ratio of 20:1 mL/g, and an amount of enzyme (cellulose/pectinase = 1:1) of 1.5%, forming H. spectabile powder. Under these conditions, the total flavonoid extraction rate in the H. spectabile leaf extract was 4.22%. AB-8 resin showed superior performance in terms of purification, and the optimal adsorption and desorption times were 1.5 h and 3 h, respectively. The recommended parameters for purification included a liquid volume of 5.5 BV, a flow rate of 1.2 BV/min, a pH of 5, and a concentration of 0.8 mg/mL. The observed order for reducing capacity was ascorbic acid (VC) > rutin > purified total flavonoids > crude extract of total flavonoids. The purified total flavonoid extract from H. spectabile showed a good scavenging ability against DPPH, ·OH, and ABTS·+, suggesting strong antioxidant activity. Therefore, this study can serve as technical support and reference data for the further development and utilization of H. spectabile resources.