This study aimed to enhance the valorization of Chaenomeles speciosa leaves as a sustainable source of bioactive phenolics. An innovative ionic liquid-based ultrasound-assisted extraction (IL-UAE) method was developed for extracting phenolic compounds. Among 10 structurally diverse ILs, [BMIM]Br demonstrated superior extraction performance. Using a combination of single-factor design and response surface methodology (RSM), the optimal parameters for IL-UAE were determined to be the [BMIM]Br concentration of 1.33 mol/L, ultrasonic power of 380 W, extraction time of 10 min, and liquid-to-solid ratio of 22 mL/g. Under these conditions, the yield of C. speciosa leaves total phenolics (CSL-TP) was 78.14 ± 0.35 mg/g, which was substantially higher than those obtained via conventional heat reflux and UAE. After extraction, the microstructures of C. speciosa leaves were examined using scanning electron microscopy (SEM), which confirmed the effectiveness of IL-UAE. Subsequently, NKA-II resin column chromatography was developed to effectively purify crude CSL-TP extracts, guided by leakage and elution curve evaluations, yielding phenolic extracts with a purity of 75.40 % ± 1.93 %. A UPLC-QqQ-MS/MS method was developed for the quantitative analysis of nine major phenolics in purified CSL-TP extracts. Furthermore, bioactivity assessments demonstrated that the purified CSL-TP extracts efficiently scavenged radicals and effectively inhibited the proliferation of HCT-116 and HT-29 cell lines. These results highlight the potential of C. speciosa leaves as a valuable resource for the pharmaceutical and food industries, paving the way for the development of innovative therapeutic products and functional foods.