Extreme marine environments act as natural screening libraries for polyextremophilic enzymes. It motivates the exploration of enzymes for biocatalysis in non-aqueous systems. Here, promiscuity of halophilic phenylalanine dehydrogenase (NTAaDH) from Natranaerobius thermophilus in the reduction of unnatural keto acids was studied. NTAaDH asymmetrically reduces a wide range of carbonyl compounds, including phenylglyoxylic acid, 2-oxobutanoic acid, 2-oxovaleric acid, phenoxy-2-propanone, 2-methylcyclohexanone, and 3-methylcyclohexanone. The results indicated NTAaDH exhibits not only amino acid dehydrogenase activity, but also amine dehydrogenase activity due to promiscuous behavior. Notably, NTAaDH exhibited excellent catalytic efficiency for 2-oxobutanoic acid at 50 ^oC. And the half-life of NTAaDH for 2-oxobutanoic acid was enhanced by 2.66-fold of that of phenylpyruvic acid. Because of the small molecular size for 2-oxobutanoic acid, the K_m of NTAaDH is smaller than that of phenylpyruvic acid, and the k_cat/K_m of NTAaDH for 2-oxobutanoic acid was enhanced by 2.16-fold of that of phenylpyruvic acid. Besides, the k_cat/K_m of NTAaDH for phenylglyoxylic acid, phenoxy-2-propanone, and 3-methylcyclohexanone was enhanced by 1.04-fold, 1.17-fold, and 1.06-fold of that of phenylpyruvic acid. As a halophilic polyextremophilic enzyme, NTAaDH is naturally adapted to the specific stress conditions, such as salinity, pH, and temperature, providing a reference for research on the promiscuity of marine halophilic enzymes and a green platform for industrial synthesis of chiral amines, unnatural amino acids with marine-relevant pharmaceutical product application.