Ocular allergy is one of the most common disorders of the eye surface. The conventional eye drops lack of therapeutic efficacy due to low ocular bioavailability and decreased drug residence time on eye surface. Hence, the present research work aimed to formulate, optimize, and evaluate the in situ gel for ophthalmic drug delivery. The prepared in situ gel formulations were evaluated for clarity, pH, gelling capacity, viscosity, osmolality, in vitro release study, and kinetic evaluation. ex vivo corneal permeation/penetration study using goat and in vivo studies on rabbits were also performed. Fourier-transformed infrared spectroscopy was also applied to study possible interactions between drug and polymers. The formulations found to be stable, nonirritant, and showed sustained release of the drug for a period of up to 24 hr with no ocular damage. The developed in situ gels loaded with tetrahydrozoline are alternative and promising ocular candidates for the treatment of allergic conjunctivitis.