The solubility profile of a weakly water-soluble drug of sertraline (SRT) at the temperature range of 298.2–318.2 K under atmospheric pressure, in the binary aqueous mixtures of dimethyl sulfoxide (DMSO) and diethylene glycol monoethyl ether (DEGMEE) was measured using a shake-flask method. As a result, SRT was discovered to have the maximum solubility in DMSO among investigated solvent systems. The obtained solubility values were correlated by utilizing cosolvency models, including the Jouyban-Acree-van’t Hoff and Jouyban-Acree models, and the mean relative deviations were computed in order to evaluate the precision of these equations. Additionally, using the van't Hoff and Gibbs formulas at Thm, the parameters of apparent thermodynamics (Gibbs energy, entropy, and enthalpy) of SRT in the saturated mixtures were calculated. According to these solubility results, SRT nanosuspensions, which had a mean particle size of under 200 nm, were formulated in DMSO and water as a solvent combination. Therapeutic development could be significantly improved by implementing solubilization strategies for enhancing the bioavailability of medicines that are only weakly water-soluble, according to the results of the experimental and statistical assessment of solubility.