Rapid, green and efficient extraction of active compounds followed by fast analysis is always pursued in the field of food analysis and/or industry. Herein, a green and highly efficient extraction of four active flavonoids from the seeds of Oroxylum indicum using a combination of natural deep eutectic solvents (DESs) and tissue-smashing extraction (TSE) technique was applied and a UPLC method was developed for their sensitive and selective quantification. RSM coupled with BBD procedure was used to optimize the extraction conditions based on single factors, such as liquid-solid ratios, extraction speed and extraction time. Compared with other conventional methods, the TSE greatly shortens extraction time, obviously raises the extraction production, and decreases energy consumption. By combination of the DES-based TSE and UPLC, the analysis of flavonoids was accomplished within only 6 min, providing an ultra-rapid, environmentally friendly and promising choice for extraction and analysis of active compounds in natural products.