A series of water-soluble half-sandwich [Cp*Rh-III((NN)-N-boolean AND)Cl](+) (Cp* = pentamethylcyclopentadiene, (NN)-N-boolean AND-substituted 2,2'-bipyridine) complexes containing electron-donating substituents around the 2,2'-bipyridyl ligand were synthesized and fully characterized for the regioselective reduction of nicotinamide coenzyme (NAD(+)). The influence of the positional effect of the substituents on the structural, electrochemical, and catalytic properties of the catalyst was systematically studied in detail. The catalytic efficiency of the substituted bipyridine Cp*RhIII complexes are inversely correlated with their redox potentials. The 5,5'-substituted bipyridine Cp*RhIII complex, which had the lowest reduction potential, most effectively regenerated NADH with a turnover frequency of 1100 h(-1). Detailed kinetic studies on the generation of intermediate(s) provide valuable mechanistic insight into this catalytic cycle and help to direct the future design strategy of corresponding catalysts.