This study was carried out to study the anti-hyperuricemic and antioxidant properties of C. colocynthis fruit pulps methanolic crude extract. The intra-peritoneal injection with 250 mg/kg/day potassium oxonate (PO) was used to develop hyperuricemic gout rat model. Our results reported that C. colocynthis pulps oral administration introduced potent hypouricemic and antioxidant properties against hyperuricemic gout rat model. The oral administration with C. colocynthis extract greatly alleviated the levels of ankle joint swelling rates (%), serum uric acid, xanthine oxidase (XOD), and thiobarbituric acid reactive substances (TBARS/MDA) as well as reduced the fold of differences of the renal mRNA URAT1 and mRNA GLUT9 urate reabsorption transports. Furthermore, C. colocynthis extract highly increased the levels and activities of serum total proteins content, glutathione peroxidase (GSHPx), and superoxide dismutase (SOD) enzymes. Moreover, Cc pulps extract greatly improved and reduced damage, inflammation and cytotoxicity in the liver and ankle joint specimens. Finally, C. colocynthis fruit pulps greatly introduced powerful therapeutic properties to improve the harmful hyperuricemia features compared to the allopurinol (Allo) administration.