Abstract <p>Piperazine is an important raw material for the production of pharmaceuticals, pesticides, polymers, and other products of organic synthesis. The dissolution and crystallization of piperazine play a key role in technological processes such as synthesis, separation of reaction mixture components, crystallization, extraction, and purification. However, data on the solubility of piperazine in organic media remain limited, which complicates the development of new processes and materials. In this work, the solubility of piperazine in a series of alcohols (<i>n</i>-butanol, 2-(<i>n</i>-butoxy)ethanol, 2-methoxyethanol, and 2-(2-methoxyethoxy)ethanol) and ethers (dimethyl ethers of diethylene glycol and triethylene glycol) was studied in the temperature range from 20 to 90°C at atmospheric pressure. Solubility was determined using the equilibrium method. The experimental data were correlated using the modified Apelblat equation, the λ<i>h</i> equation, and the van’t Hoff equation. For most of the investigated organic media, the λ<i>h</i> equation provided the best agreement with the experimental results. The results show that the solubility of piperazine increases with increasing temperature. In addition, the standard thermodynamic parameters of dissolution, including enthalpy, entropy, and Gibbs energy, were calculated using the van’t Hoff equation. The thermodynamic analysis confirms that the dissolution of piperazine is an endothermic process driven primarily by an increase in entropy. The obtained data can be used to model and optimize processes in the chemical and pharmaceutical industries, predict the behavior of piperazine in multicomponent systems, and support further research in solution thermodynamics and the development of new piperazine-based materials.</p>