This study evaluates the application of eco-friendly deep eutectic solvents (DESs) in the extraction of phenolic antioxidants from dogbane leaf-tea (DLT). The results showed DESs with lower viscosity allowed an efficient extraction of significantly higher contents of total phenolics or flavonoids. An innovative and high-efficient solvent, choline chloride-levulinic acid (ChCl-LevA), was screened and used in ultrasonic-assisted extraction (UAE) of phenolic compounds from DLT. According to full factorial design experimental results, total phenolic content (TPC), total flavonoid content (TFC), antioxidant activity, and anti-α-glucosidase activity (α-GIA) of the DLT extracts were simultaneously optimized by response surface methodology. Sonication temperature and water content in ChCl-LevA were found to be the major factors affecting the TPC, TFC, antioxidant activity, and α-GIA of DLT extracts. Under the optimum parameters (water content in ChCl-LevA was 45%, sonication temperature was 50 °C, and extraction time was 30 min), the measured results for all the responses were obtained as follows: TPC-91.38 ± 7.20 mg GAE/g DW, TFC-84.12 ± 3.47 mg RE/g DW, ABTS+-492 ± 7.33 mmol TE/g DW, FRAP-6235 ± 121 μmol Fe(II)/g DW and α-GIA-230 ± 7.59 mmol AE/g DW, which were consistent with the predicted values. In addition, strongly significant positive correlations were observed between TPC/TFC and bio-activities of the DLT extracts. HPLC results indicated high contents of (-)-epigallocatechin (4272 ± 84.86 μg/g DW), catechin (5268 ± 24.53 μg/g DW), isoquercitrin (3500 ± 86.07 μg/g DW), kaempferol 3-O-rutinoside (3717 ± 97.71 μg/g DW), and protocatechuic acid (644 ± 1.65 μg/g DW) were observed in the DLT extracts. In contrast to other extraction methods, ChCl-LevA-based UAE yielded higher TPC, TFC, individual phenolic contents, stronger antioxidant activity, and α-GIA. Scanning electron microscope (SEM) analysis further confirmed that ChCl-LevA-based UAE enhanced the disruption of cell wall structure, thereby making more phenolic antioxidants released from DLT. In short, ChCl-LevA-based UAE was confirmed to be an innovative and high-efficient method for extraction of phenolic antioxidants from DLT. Dogbane leaves can be considered as a good tea source rich in natural antioxidants.