Escitalopram (ETP) has poor oral bioavailability due to its low water solubility, hence the goal of this work was to design and optimize a self-nano-emulsifying drug delivery system (SNEDDS). Using the results of the investigations on solubility and emulsification, a pseudo-ternary phase diagram was produced. The three main ingredients chosen for the formulation were polyethylene glycol 400 (co-surfactant), tween 80 (surfactant), and geranium oil (lipid). ETP-SNEDDS was evaluated for the size of particles and surface charge. Fourier transforms infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to evaluate the chemical compatibility and thermal stability. Ex-vivo permeability, in vitro digestion, and in vitro dissolution investigations were carried out and compared with reference tablets. The bioavailability of ETP-loaded SNEDDS was evaluated in comparison to the control in Wistar rats (n = 6). With a droplet size of 145 nm, a polydispersity index of 0.120, and an emulsification period of almost one minute, the synthesized SNEDDS were thermodynamically stable. The ETP-loaded SNEDDS displayed 96% dissolution in FSSIF. The permeation investigation revealed that, in comparison to the ETP powder and reference tablet, respectively, the SNEDDS increased drug penetration by 4.2 and 3.1-folds. The enhancement of in vitro dissolution, in vitro digestion, and ex-vivo permeability was found significant (p < 0.05). In comparison to the reference, SNEDDS had Cmax and AUC increases of 5.34 and 4.71 fold, respectively. These findings suggested that the SNEDDS formulation would be a promising method for increasing the oral bioavailability and absorption of ETP.