The present work reports a novel green synthesis of CuO nanoparticles (CuONPs) exerting an extract of the Hymenocrater Platystegius plant as a mild and non-toxic stabilizing agent. In order to obtain its applicability, a carbon paste electrode (CPE) was modified with the CuONPs and graphene oxide (GO) (CuONPs/GO/CPE) for trace determination of histamine (HIS) and uric acid (UA). The electrochemical investigations on HIS and UA were accomplished by the application of differential pulse voltammetry (DPV), cyclic voltammetry (CV), and chronoamprometry (CA) methods. The results showed the modified electrode expedites the electron transfer reactions of HIS and UA. The modified electrode exhibited some advantages such as good stability, convenient preparation, and high sensitivity toward HIS and UA determination. Under the optimum conditions, the electrode provides a linear response versus HIS and UA concentrations in the range of 1-300 and 0.5-500 µM, with a detection limit of 0.94 µM and 0.25 µM (S/N=3), respectively. The electrochemical results recommended that the CuONPs/GO/CPE is a promising sensor to determine HIS and UA in real samples with a significant recovery.