The demand for sustainable extraction methods has led to the development of Natural Deep Eutectic Solvents (NADES) as efficient alternatives to enhance the yield of bioactive compounds from plants. This study evaluated Oroxylum indicum fruit as a source of baicalin, employing NADES and ultrasound-assisted extraction (UAE) to improve the efficiency. Among the 14 NADES formulations, NPBC (L-proline, 1,4-butanediol, and choline chloride) achieved the highest baicalein yield. Optimization through response surface methodology identified the ideal conditions—37 min, 65 °C, and 40% water—resulting in a baicalein yield over 2.5 times greater than with 70% ethanol. Bioactivity assays, including DPPH and LPS-stimulated RAW macrophage tests, demonstrated that the NPBC extract had potent antioxidant and anti-inflammatory effects, significantly inhibiting nitric oxide (NO) production and downregulating inflammatory genes (iNOS, IL-6, COX-2, 5-LOX) to baseline levels. This NADES-UAE approach markedly enhances the extraction efficiency and converts baicalin to baicalein, boosting the pharmacological potential of plant extracts while providing a sustainable alternative to traditional methods.