A thermostated reactor and UV–visible spectrophotometer analysis were used to determine the solubility of emodin and aloe-emodin, two naturally occurring compounds with pharmacological activity. At a pressure of 0.1 MPa under atmospheric conditions, and temperatures from 283.15 to 323.15 K with intervals of 5 K, the solubility in different water–ethanol combinations was the primary focus of the investigation. Under constant solvent composition, a positive correlation was observed between the solubility of emodin/ or aleo-emodin and the experimental temperature in all examined mixed solvent systems. To better understand the relationships between solutes and solvents and the interactions between several solvents, the KAT-LSER model was used to conduct multiple linear regression analysis on systems containing either pure solvents or a combination of solvents. In addition, several thermodynamic models were used to establish a connection with the empirical solubility data. These models included the Jouyban-Acree, Apelblat-Jouyban-Acree, van’t Hoff-Jouyban-Acree, and Ma models. The correlation findings demonstrate that all four thermodynamic models accurately predicted emodin and aleo-solubility emodin’s behavior under different solvent and temperature settings. Furthermore, the thermodynamic characteristics of emodin solubility in binary solvent combinations were determined using the van’t Hoff model. According to the findings, two compounds were found to undergo endothermic and non-spontaneous dissolution.