The <em>Citrullus colocynthis (L.) Schard</em> from Cucurbitaceae family having a properties of ancient remedies on many diseases. This research work has focused on the to detect the preliminary antacid test (PAT), acid neutralizing capacity (ANC) ,buffer capacity(BC) consisting of <em>Citrullus colocynthis </em>and compared with Gelusil tablet as a standard along with this determined the immunomodulation activity. The PAT of the ethyl acetate,aqueous and alcoholic extracts of fruit were found in range of pH 3.90 ± 0.07 to 6.36 ± 0.18 and ANC located in between 24.23 ± 00 to 27.86 ± 76 mEq/gm. Further the value at which the pH of an extracts changes over period founded in between 30 min to 45 min. The investigation of immunomodulation activity carried out by phagocytosis assay of <em>C. albican</em>. This research has reached to conclusion that is the ethanolic extract yielded a greater result of ANC and aqueous extract determined higher buffer capacity comparative with standard antacid (Gelusil). Moderate immune stimulation shown by the ethanolic extract with 5 and 10 mg/ml of concentration.