In this study, a Ni-Fe metal-organic framework modified by –NH2 and –SH was synthesized using a simple hydrothermal process for enhancing photocatalytic CO2 reduction. As expected, the N2S-NiFe (NH2-BDC/H4DSBDC, 2:1) displayed excellent photocatalytic CO2 reduction activity and high CO selectivity (12,412.23 μmol g−1 h−1) under visible light irradiation (λ ≥ 420 nm), which is 5 times that of NiFe-MOF. Notably, the excellent photocatalytic performance of N2S-NiFe can benefit from the rich defect trap site caused by the introduction of amino and sulfhydryl groups, accelerating charge transfer and promoting space charge separation, as supported by the photo-electrochemical properties. To better understand the CO2 adsorption mechanism, density functional theory calculations were performed, which revealed that the Niov site has more negative adsorption energy compared with the Feov site. This study provides a simple strategy to establish efficient photocatalysts for CO2 reduction through the modification of organic ligands.