Present work is aimed at development and characterization of phytosomes, novel drug delivery dosage form used to improve the bioavailability of the drug, containing ethanolic, aqueous, dichloromethane and ethyl acetate extract of Citrullus colocynthis to meet the need for better effectiveness and safety. Required phytosomal formulations were developed using different extracts of Citrullus colocynthis and phytosomes formed from the lecithin and cholesterol, then characterized. Characterization involved various parameters, such as Particle size determination, apparent solubility, entrapment efficiency, Scanning Electron Microscope, Fourier-Transform Infrared Spectroscopy, X-ray Diffraction (XRD), and dissolution study (in-vitro drug release). Particle size varied from 250 nm to 0.1 µm depending on the extract. The mean particle size of phytosomal complex of DCM extract of CC was scattered in a narrow range of 254 ± 20.0 nm, and polydispersity index was 0.857 ± 0.055, where phytosomal formulation of DCM extract shows better entrapment then other phytosomal formulation. Photomicrographs revealed that phytosomes were spherical in shape and uniform in size.