Abstract: Deep eutectic solvents (DESs), as a new type of green solvent, have shown great advantages of easy preparation, no purification needed after synthesis and great potential for application in various fields. A new type of drug delivery system called therapeutic deep eutectic solvent (THEDES) was developed when combining active pharmaceutical ingredients (APIs) into DES. Matrine has been shown great potential applications due to its anti-inflammatory, antioxidant, and antibacterial functions. This paper constructed a series of new THEDES based on matrine and fatty acids, and deeply studied the effects of alkyl chain length of fatty acids, the molar ratio of hydrogen bond donor (HBD) to hydrogen bond receptor (HBA) on the physicochemical properties of DES. The results showed that the density, surface tension, conductivity and polarity of DES declined with the increase of alkyl chain length of fatty acids, while the viscosity of DES increased with the increase of chain length of fatty acids. In addition, the density, surface tension and viscosity declined with the decrease of the molar ratio of matrine to fatty acid, while the conductivity increased with the decrease of the molar ratio of matrine to fatty acid. These different trends were due to the changes in the interaction between matrine and fatty acid molecules. The results of this work provided an important basis for the development and application of matrine-based therapeutic eutectic solvents.