This study evaluated the purifying effect of the zinc oxide-Chromolaena odorata (ZnO-CO) nanoparticle on water samples collected from Oyun River water. Physicochemical and bacteriological characteristics of untreated and treated Oyun river water were determined and their effects on hematological parameters, liver and kidney of rats were also investigated. Thirty-two albino rats (with mean weight ± SD of 132.00 ± 7.50g) were randomized into four groups (A-D). Rats in groups A, B, C and D were maintained on distilled water, untreated Oyun river water (UW), ZnO-CO-treated Oyun river water (ZW), and alum-treated Oyun river water (AW), respectively for 30 days. Thermo-tolerant and enteric bacteria were undetectable in UW samples after treatment with the ZnO-CO nanoparticle. WBC, RBC and platelet counts of rats maintained on UW, ZW, and AW were significantly different from those in the control. Liver aspartate aminotransferase (AST), alanine aminotransferase (ALT) and acid phosphatase (ACP) activities of rats maintained on ZW were increased significantly (p<0.05) when compared to the control. Serum globulin and creatinine concentrations of rats maintained on ZW also increased significantly when compared with the control. The results of this study suggest that Oyun river water is polluted, and its consumption may produce deleterious effects in humans. Treatment of Oyun river water with the synthesized ZnO-CO nanoparticle is more effective than alum in purifying the polluted water. However, ZW also impacted negatively on the liver and renal functions of rats. Hence, ZnO-CO nanoparticle treated water may not be safe as drinking water.