The aim of current study is to synthesis novel visible driven photocatalysts (L-Histidine (C, N) codoped-TiO2-CdS) with different loadings of L-Hisitdine (1, 2, and 3 wt.%) and CdS (1:9, 7:1, and 1:5 mass ratios of CdS to TiO2). Then, their application for photo-degradation of methyl orange (MO) and biologically treated palm oil mill effluent (POME) were studied. The structure, optical properties, and morphology of the prepared nano composites were also characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), Fourier transform infrared (FT-IR), photoluminescence spectroscopy (PL), and diffuse reflectance spectra (DRS). DRS results indicated that all the modified samples with different L-Hisitdine and CdS loadings showed a red shift to visible region. The results of photo-degradation experiments showed that L-Hisitdine with a weight fraction of 2% and mass ratio of TiO2 to CdS of 7:1 were the optimum amount of the modifiers in the photo catalyst network. The PL intensity of the photocatalyst decreased with addition of L-Hisitdine and CdS nano particles due to a decrease in e(-)/h(+) recombination. The effects of organic pollutant concentration, initial pH, catalyst concentration, and irradiation time on the photo-degradation process of MO and POME were studied using full faced centered central composite design (CCFD) under response surface methodology (RSM). The obtained results showed that MO was completely removed at initial concentration of 10 mg/L, acidic pH, and catalyst loading of 1.5 g/L after 120 min. The complete degradation of biologically treated POME was achieved at original pH, 300 mg/L of chemical oxygen demand (COD) concentration, catalyst loading of 2 g/L, and irradiation time of 2 h.