Background: Co-crystals have been highly promising for tailoring physicochemical properties of Active pharmaceutical ingredient (API) by coupling with co-former. Objectives: The objective of the present work was to prepare and characterize novel nano co-crystals of Ezetimibe by different methods in various ratios of co-formers and to optimize the formulation based on the enhancement in solubility and dissolution rate. Methods: Ezetimibe nano co-crystals were prepared employing oxalic acid, succinic acid and maleic acid as co-formers by solvent evaporation method and anti-solvent method. Results: Instrumental analysis of co-crystals (DSC, IR, SEM and XRD) was performed to characterize the novel nano co-crystals. Dissolution studies and chemical stability were assessed and compared with pure Ezetimibe. The formulation with maleic acid as a co-former in the molar ratio of Ezetimibe and maleic acid (0.4:0.4) was found to be efficient than oxalic acid and succinic acid. The co-crystal dissolution profile in distilled water containing 0.5% SLS showed 18.8 folds increase in the dissolution efficiency and was found to be 95.2% within 45 min. Conclusion: The results demonstrate feasibility of co-crystallization method using maleic acid as co-former to enhance the solubility of poorly soluble drug Ezetimibe.