Xue–Zhi–Ning (XZN) is a traditional Chinese medicine formula, containing active ingredients with poor solubility in water, which has been demonstrated to be helpful for patients with hyperlipidemia. One-pot β-cyclodextrin (β-CD)-assisted extraction of active ingredients from XZN has been carried out to develop an efficient and eco-friendly extraction process. Five active compounds—rubrofusarin gentiobioside, 2,3,5,4′-tetrahydroxy-stilbene-2-O-β-D-glucoside, emodin, nuciferine and quercetin—were identified by UPLC/DAD/MS and used as indexes to evaluate the process optimized by an orthogonal test. The results showed that addition of β-CD significantly enhanced the extraction ratios of all five components. The enhancement of extraction ratios was positively correlated with the apparent formation constants between β-CD and the compounds. The study also showed that the stabilities and dissolution rates of the active ingredients were improved in the presence of β-CD. This one-pot β-cyclodextrin-assisted extraction has the potential to be applied in pharmaceutical preparations directly.