In this study, a switchable temperature-responsive ionic liquid-based surfactant-free microemulsion (TRIL-SFME) for extraction and in-situ separation of hydrophilic and lipophilic compounds from Camptotheca acuminata was firstly developed and systematically characterized. This TRIL-SFME was obtained using 1-hexyl-3-methylimidazolium tetrafluoroborate ([HMIM][BF4]), 1,2-propanediol and H2O. The prepared TRIL-SFME presented low viscosity and rapid response to temperature. Firstly, the effect of temperatures on TRIL-SFME phase behavior was studied followed by determination of effect of liquid/solid ratio and extraction time on the extraction yields of the targeted compounds. The TRIL-SFME demulsified rapidly by thermal stimulus, resulting in in-situ separation and enrichment of compounds with varying polarity. The results of present study revealed that TRIL-SFME had higher extraction yields (1.50–5.79 folds) compared to traditional solvents and individual components of TRIL-SFME. Besides, in-situ separation and enrichment of hydrophilic compounds (phenolic acids) and lipophilic compounds (alkaloids) was accomplished in short time (within 3 min) by cooling the system to 4 ℃. Furthermore, the mesoscopic behavior between TRIL-SFME and targeted compounds was simulated by dissipative particle dynamics (DPD) to explore the extraction mechanism for the first time. The results illustrated the formation of W/IL structure of TRIL-SFME and clarified solubilization mechanism of TRIL-SFME system for targeted compounds, which is related to its special "water pool" structure. This novel and switchable TRIL-SFME is an environmentally friendly and promising alternative to simultaneously extract, in-situ separate and enrich the natural active compounds with different polarity from plant matrices.