Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability, ocular inflammation, and visual discomfort. Increasing interest in herbal medicines has encouraged the exploration of plantderived compounds as potential therapeutic agents with fewer side effects. The present study aimed to investigate the pharmacognostical, phytochemical, and in silico therapeutic potential of Cocculushirsutus (L.) W. Theob. leaves against molecular targets associated with dry eye disease. Fresh leaves of Cocculushirsutus were collected, authenticated, and subjected to pharmacognostical evaluation including macroscopic, microscopic, and powder microscopy studies. Physicochemical parameters such as ash values, extractive values, loss on drying, and foaming index were determined to establish quality control standards. The powdered leaves were extracted using Soxhlet extraction with hydroalcoholic solvent, and preliminary phytochemical screening was performed to identify major secondary metabolites. GC–MS analysis was conducted to identify bioactive compounds present in the extract. In silico pharmacological studies including ADME prediction and molecular docking analysis were carried out to evaluate drug-likeness and binding affinity of the identified phytoconstituents against target proteins associated with dry eye disease (PDB IDs: 9K25 and 5E6R). Pharmacognostical studies revealed characteristic morphological and anatomical features of the plant, while physicochemical evaluation confirmed the purity and quality of the crude drug. Phytochemical screening indicated the presence of alkaloids, flavonoids, phenolic compounds, glycosides, terpenoids, amino acids, and saponins. GC–MS analysis identified several bioactive constituents including octanoic acid ethyl ester, 3-methylsalicylic acid, dodecanoic acid ethyl ester, inositol-1-deoxy, tetrahydrofurfuryl propionate, and phenol 2,4-bis (1,1-dimethyl ethyl) phosphite. ADME analysis demonstrated favorable drug-likeness properties for most compounds according to Lipinski’s rule of five. Molecular docking results revealed that phenol 2,4-bis (1,1-dimethyl ethyl) phosphite and adamantane-1-carboxamide exhibited significant binding affinity toward the target proteins, comparable to the standard drug lifitegrast. These findings suggest that Cocculushirsutus possesses promising bioactive compounds with potential therapeutic applications in the management of dry eye disease. However, further in vitro and in vivo studies are required to validate these results and confirm their clinical applicability