The purpose of this study based upon design and synthesis of a new series of 1,4- disubstituted piperazine-2,3-dione derivatives through two steps reaction. This protocol involves the formation of N,N\-Bis-(4-substituted benzyl)-ethane-1,2-diamine and N,N\-Bis-[1- (4-substituted phenyl)-ethyl]-ethane-1,2-diamine derivatives (1a-i) through reductive alkylation reaction from ethylenediamine and different carbonyl compounds in the presence of sodium cyanoborohydride. The second step involves reaction of compounds (1a-i) with diethyl oxalate affording the target compounds. Consequently, nine new 1,4-disubstituted piperazine-2,3-dione derivatives were synthesized as the target compounds, 1,4-Bis-(4-substituted benzyl)- piperazine-2,3-dione and 1,4-Bis-[1-(4-substituted phenyl)-ethyl]-piperazine-2,3-dione derivatives (2a-i). The structures of the target compounds were elucidated depending upon the data of the different spectral as well as the elemental methods of analyses. In addition, a mass spectrum, for a representative example, was carried out where the expected fragmentation pattern is in accordance with the structure of the considered compound. The lipophilicity of the target compounds as expressed from the ClogP and the measured R f remarkably supercede that of piperazine. The preliminary anthelmintic activity of the newly synthesized derivatives (2a-i) was investigated in vitro against Enterobiuos vermicularis and Fasciola hepatica. The tested compounds exhibited, in all cases, considerable inhibitory effects on the growth of the tested parasites in comparison with piperazine hydrate as a reference drug.